Estrogen receptor mutations in human disease

Endocrine Reviews

Volumn 25, Issue 6, 2004, Pages 869-898

  Herynk, Matthew H ^a   Fuqua, Suzanne A W ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; ESTROGEN RECEPTOR; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA;

5' UNTRANSLATED REGION; BREAST CANCER; BREAST CARCINOGENESIS; ENDOMETRIUM CANCER; ESTROGEN ACTIVITY; EXON; HUMAN; MENTAL DISEASE; MOLECULAR CLONING; MUTAGENESIS; MUTATION; POINT MUTATION; PRIORITY JOURNAL; REVIEW; RNA SPLICING;

ALTERNATIVE SPLICING; DISEASE; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; EXONS; HUMANS; MUTATION; POINT MUTATION; RNA SPLICING; RNA, MESSENGER;

EID: 10644274482     PISSN: 0163769X     EISSN: None     Source Type: Journal    
DOI: 10.1210/er.2003-0010     Document Type: Review

References (407)

1. Cyr M, Calon F, Morissette M, Di Paolo T 2002 Estrogenic modulation of brain activity: implications for schizophrenia and Parkinson's disease. J Psychiatry Neurosci 27:12-27
2. Gennari L, Becherini L, Falchetti A, Masi L, Massart F, Brandi ML 2002 Genetics of osteoporosis: role of steroid hormone receptor gene polymorphisms. J Steroid Biochem Mol Biol 81:1-24
3. Grumbach MM 2000 Estrogen, bone, growth and sex: a sea change in conventional wisdom. J Pediatr Endocrinol Metab 13(Suppl 6):1439-1455
4. Russo IH, Russo J 1998 Role of hormones in mammary cancer initiation and progression. J Mammary Gland Biol Neoplasia 3:49-61
5. Di Leo A, Messa C, Cavallini A, Linsalata M 2001 Estrogens and colorectal cancer. Curr Drug Targets Immune Endocr Metabol Disord 1:1-12
6. Pujol P, Rey JM, Nirde P, Roger P, Gastaldi M, Laffargue F, Rochefort H, Maudelonde T 1998 Differential expression of estrogen receptor-α and -β messenger RNAs as a potential marker of ovarian carcinogenesis. Cancer Res 58:5367-5373
7. Feigelson HS, Ross RK, Yu MC, Coetzee GA, Reichardt JK, Henderson BE 1996 Genetic susceptibility to cancer from exogenous and endogenous exposures. J Cell Biochem Suppl 25:15-22
8. Colditz GA 1998 Relationship between estrogen levels, use of hormone replacement therapy, and breast cancer. J Natl Cancer Inst 90:814-823
9. Beatson C 1896 On the treatment of inoperable cases of carcinoma of the mamma: suggestions for a new method of treatment, with illustrative cases. Lancet 2:104-107
10. Boyd S 1900 On oophorectomy in cancer of the breast. Br Med J 2:1161-1167
11. Jensen E, Jacobson HI 1960 Fate of steroidal estrogens in target tissues. In: Pincus G, Vollmer EP, eds. Biological activities of steroids in relation to cancer. New York: Academic Press; 161-174
12. Jensen E, Jacobson HI 1962 Basic guides to the mechanism of estrogen action. Recent Prog Horm Res 18:387-414
13. Toft D, Gorski J 1966 A receptor molecule for estrogens: isolation from the rat uterus and preliminary characterization. Proc Natl Acad Sci USA 55:1574-1581
14. Toft D, Shyamala G, Gorski J 1967 A receptor molecule for estrogens: studies using a cell-free system. Proc Natl Acad Sci USA 57:1740-1743
15. Gorski J, Toft D, Shyamala G, Smith D, Notides A 1968 Hormone receptors: studies on the interaction of estrogen with the uterus. Recent Prog Horm Res 24:45-80
16. Jensen EV, Suzuki T, Kawashima T, Stumpf WE, Jungblut PW, DeSombre ER 1968 A two-step mechanism for the interaction of estradiol with rat uterus. Proc Natl Acad Sci USA 59:632-638
17. Walter P, Green S, Greene G, Krust A, Bornert JM, Jeltsch JM, Staub A, Jensen E, Scrace G, Waterfield M, Chambon P 1985 Cloning of the human estrogen receptor cDNA. Proc Natl Acad Sci USA 82:7889-7893
18. Green S, Walter P, Kumar V, Krust A, Bornert JM, Argos P, Chambon P 1986 Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature 320:134-139
19. Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, Shine J 1986 Sequence and expression of human estrogen receptor complementary DNA. Science 231:1150-1154
20. Green S, Walter P, Greene G, Krust A, Goffin C, Jensen E, Scrace G, Waterfield M, Chambon P 1986 Cloning of the human oestrogen receptor cDNA. J Steroid Biochem 24:77-83
21. Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA 1996 Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 93:5925-5930
22. Tremblay GB, Tremblay A, Copeland NG, Gilbert DJ, Jenkins NA, Labrie F, Giguere V 1997 Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor β. Mol Endocrinol 11:353-365
23. Mosselman S, Polman J, Dijkema R 1996 ER β: identification and characterization of a novel human estrogen receptor. FEBS Lett 392:49-53
24. Enmark E, Pelto-Huikko M, Grandien K, Lagercrantz S, Lagercrantz J, Fried G, Nordenskjold M, Gustafsson JA 1997 Human estrogen receptor β-gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab 82:4258-4265
25. Ogawa S, Inoue S, Watanabe T, Hiroi H, Orimo A, Hosoi T, Ouchi Y, Muramatsu M 1998 The complete primary structure of human estrogen receptor β (hER β) and its heterodimerization with ERα in vivo and in vitro. Biochem Biophys Res Commun 243:122-126
26. Moore JT, McKee DD, Slentz-Kesler K, Moore LB, Jones SA, Horne EL, Su JL, Kliewer SA, Lehmann JM, Willson TM 1998 Cloning and characterization of human estrogen receptor β isoforms. Biochem Biophys Res Commun 247:75-78
27. Speirs V, Malone C, Walton DS, Kerin MJ, Atkin SL 1999 Increased expression of estrogen receptor β mRNA in tamoxifen-resistant breast cancer patients. Cancer Res 59:5421-5424
28. Speirs V, Parkes AT, Kerin MJ, Walton DS, Carleton PJ, Fox JN, Atkin SL 1999 Coexpression of estrogen receptor α and β: poor prognostic factors in human breast cancer? Cancer Res 59:525-528
29. Dotzlaw H, Leygue E, Watson PH, Murphy LC 1997 Expression of estrogen receptor-β in human breast tumors. J Clin Endocrinol Metab 82:2371-2374
30. Dotzlaw H, Leygue E, Watson PH, Murphy LC 1999 Estrogen receptor-β messenger RNA expression in human breast tumor biopsies: relationship to steroid receptor status and regulation by progestins. Cancer Res 59:529-532
31. Campbell-Thompson M, Lynch IJ, Bhardwaj B 2001 Expression of estrogen receptor (ER) subtypes and ERβ isoforms in colon cancer. Cancer Res 61:632-640
32. Foley EF, Jazaeri AA, Shupnik MA, Jazaeri O, Rice LW 2000 Selective loss of estrogen receptor β in malignant human colon. Cancer Res 60:245-248
33. Rutherford T, Brown WD, Sapi E, Aschkenazi S, Munoz A, Mor G 2000 Absence of estrogen receptor-β expression in metastatic ovarian cancer. Obstet Gynecol 96:417-421
34. Lubahn DB, Moyer JS, Golding TS, Couse JF, Korach KS, Smithies O 1993 Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc Natl Acad Sci USA 90:11162-11166
35. Korach KS 1994 Insights from the study of animals lacking functional estrogen receptor. Science 266:1524-1527
36. Haynes MP, Russell KS, Bender JR 2000 Molecular mechanisms of estrogen actions on the vasculature. J Nucl Cardiol 7:500-508
37. Krege JH, Hodgin JB, Couse JF, Enmark E, Warner M, Mahler JF, Sar M, Korach KS, Gustafsson JA, Smithies O 1998 Generation and reproductive phenotypes of mice lacking estrogen receptor β. Proc Natl Acad Sci USA 95:15677-15682
38. Couse JF, Curtis SW, Washburn TF, Lindzey J, Golding TS, Lubahn DB, Smithies O, Korach KS 1995 Analysis of transcription and estrogen insensitivity in the female mouse after targeted disruption of the estrogen receptor gene. Mol Endocrinol 9:1441-1454
39. Korach KS, Couse JF, Curtis SW, Washburn TF, Lindzey J, Kimbro KS, Eddy EM, Migliaccio S, Snedeker SM, Lubahn DB, Schomberg DW, Smith EP 1996 Estrogen receptor gene disruption: molecular characterization and experimental and clinical phenotypes. Recent Prog Horm Res 51:159-186; discussion 186-188
40. Schomberg DW, Couse JF, Mukherjee A, Lubahn DB, Sar M, Mayo KE, Korach KS 1999 Targeted disruption of the estrogen receptor-α gene in female mice: characterization of ovarian responses and phenotype in the adult. Endocrinology 140:2733-2744
41. Bocchinfuso WP, Korach KS 1997 Mammary gland development and tumorigenesis in estrogen receptor knockout mice. J Mammary Gland Biol Neoplasia 2:323-334
42. Eddy EM, Washburn TF, Bunch DO, Goulding EH, Gladen BC, Lubahn DB, Korach KS 1996 Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility. Endocrinology 137:4796-4805
43. Hess RA, Bunick D, Lee KH, Bahr J, Taylor JA, Korach KS, Lubahn DB 1997 A role for oestrogens in the male reproductive system. Nature 390:509-512
44. Ogawa S, Lubahn DB, Korach KS, Pfaff DW 1997 Behavioral effects of estrogen receptor gene disruption in male mice. Proc Natl Acad Sci USA 94:1476-1481
45. Ogawa S, Taylor JA, Lubahn DB, Korach KS, Pfaff DW 1996 Reversal of sex roles in genetic female mice by disruption of estrogen receptor gene. Neuroendocrinology 64:467-470
46. Ogawa S, Eng V, Taylor J, Lubahn DB, Korach KS, Pfaff DW 1998 Roles of estrogen receptor-α gene expression in reproduction-related behaviors in female mice. Endocrinology 139:5070-5081
47. Ogawa S, Washburn TF, Taylor J, Lubahn DB, Korach KS, Pfaff DW 1998 Modifications of testosterone-dependent behaviors by estrogen receptor-α gene disruption in male mice. Endocrinology 139:5058-5069
48. Rissman EF, Early AH, Taylor JA, Korach KS, Lubahn DB 1997 Estrogen receptors are essential for female sexual receptivity. Endocrinology 138:507-510
49. Wersinger SR, Sannen K, Villalba C, Lubahn DB, Rissman EF, De Vries GJ 1997 Masculine sexual behavior is disrupted in male and female mice lacking a functional estrogen receptor α gene. Horm Behav 32:176-183
50. Rubanyi GM, Freay AD, Kauser K, Sukovich D, Burton G, Lubahn DB, Couse JF, Curtis SW, Korach KS 1997 Vascular estrogen receptors and endothelium-derived nitric oxide production in the mouse aorta. Gender difference and effect of estrogen receptor gene disruption. J Clin Invest 99:2429-2437
51. Iafrati MD, Karas RH, Aronovitz M, Kim S, Sullivan Jr TR, Lubahn DB, O'Donnell Jr TF, Korach KS, Mendelsohn ME 1997 Estrogen inhibits the vascular injury response in estrogen receptor α-deficient mice. Nat Med 3:545-548
52. Karas RH, Hodgin JB, Kwoun M, Krege JH, Aronovitz M, Mackey W, Gustafsson JA, Korach KS, Smithies O, Mendelsohn ME 1999 Estrogen inhibits the vascular injury response in estrogen receptor β-deficient female mice. Proc Natl Acad Sci USA 96:15133-15136
53. Windahl SH, Andersson G, Gustafsson JA 2002 Elucidation of estrogen receptor function in bone with the use of mouse models. Trends Endocrinol Metab 13:195-200
54. Windahl SH, Hollberg K, Vidal O, Gustafsson JA, Ohlsson C, Andersson G 2001 Female estrogen receptor β -/- mice are partially protected against age-related trabecular bone loss. J Bone Miner Res 16:1388-1398
55. Wang L, Andersson S, Warner M, Gustafsson JA 2003 Estrogen receptor (ER) β knockout mice reveal a role for ERβ in migration of cortical neurons in the developing brain. Proc Natl Acad Sci USA 100:703-708
56. Lindberg MK, Moverare S, Skrtic S, Gao H, Dahlman-Wright K, Gustafsson JA, Ohlsson C 2003 Estrogen receptor (ER)-β reduces ERα-regulated gene transcription, supporting a "ying yang" relationship between ERα and ERβ in mice. Mol Endocrinol 17:203-208
57. McCauley LK, Tozum TF, Kozloff KM, Koh-Paige AJ, Chen C, Demashkieh M, Cronovich H, Richard V, Keller ET, Rosol TJ, Goldstein SA 2003 Transgenic models of metabolic bone disease: impact of estrogen receptor deficiency on skeletal metabolism. Connect Tissue Res 44(Suppl 1):250-263
58. Couse JF, Korach KS 1999 Estrogen receptor null mice: what have we learned and where will they lead us? Endocr Rev 20:358-417
59. Palmieri C, Cheng GJ, Saji S, Zelada-Hedman M, Warri A, Weihua Z, Van Noorden S, Wahlstrom T, Coombes RC, Warner M, Gustafsson JA 2002 Estrogen receptor β in breast cancer. Endocr Relat Cancer 9:1-13
60. Fuqua SA 2001 The role of estrogen receptors in breast cancer metastasis. J Mammary Gland Biol Neoplasia 6:407-417
61. Ali S, Coombes RC 2000 Estrogen receptor α in human breast cancer: occurrence and significance. J Mammary Gland Biol Neoplasia 5:271-281
62. Sommer S, Fuqua SA 2001 Estrogen receptor and breast cancer. Semin Cancer Biol 11:339-352
63. Ho KJ, Liao JK 2002 Normuclear actions of estrogen. Arterioscler Thromb Vasc Biol 22:1952-1961
64. Lannigan DA 2003 Estrogen receptor phosphorylation. Steroids 68:1-9
65. Klinge CM 2000 Estrogen receptor interaction with co-activators and co-repressors. Steroids 65:227-251
66. Tremblay GB, Giguere V 2002 Coregulators of estrogen receptor action. Crit Rev Eukaryot Gene Expr 12:1-22
67. Jordan VC 2003 Antiestrogens and selective estrogen receptor modulators as multifunctional medicines. 2. Clinical considerations and new agents. J Med Chem 46:1081-1111
68. Jordan VC 2003 Antiestrogens and selective estrogen receptor modulators as multifunctional medicines. 1. Receptor interactions. J Med Chem 46:883-908
69. Ponglikitmongkol M, Green S, Chambon P 1988 Genomic organization of the human oestrogen receptor gene. EMBO J 7:3385-3388
70. Gosden JR, Middleton PG, Rout D 1986 Localization of the human oestrogen receptor gene to chromosome 6q24-q27 by in situ hybridization. Cytogenet Cell Genet 43:218-220
71. Green S, Kumar V, Krust A, Walter P, Chambon P 1986 Structural and functional domains of the estrogen receptor. Cold Spring Harb Symp Quant Biol 51(Pt 2):751-758
72. Ribeiro RC, Kushner PJ, Baxter JD 1995 The nuclear hormone receptor gene superfamily. Annu Rev Med 46:443-453
73. Kumar V, Green S, Stack G, Berry M, Jin JR, Chambon P 1987 Functional domains of the human estrogen receptor. Cell 51:941-951
74. Berry M, Metzger D, Chambon P 1990 Role of the two activating domains of the oestrogen receptor in the cell-type and promoter-context dependent agonistic activity of the anti-oestrogen 4-hydroxytamoxifen. EMBO J 9:2811-2818
75. Metzger D, Ali S, Bornert JM, Chambon P 1995 Characterization of the amino-terminal transcriptional activation function of the human estrogen receptor in animal and yeast cells. J Biol Chem 270:9535-9542
76. Klein-Hitpass L, Ryffel GU, Heitlinger E, Cato AC 1988 A 13 bp palindrome is a functional estrogen responsive element and interacts specifically with estrogen receptor. Nucleic Acids Res 16:647-663
77. Tzukerman MT, Esty A, Santiso-Mere D, Danielian P, Parker MG, Stein RB, Pike JW, McDonnell DP 1994 Human estrogen receptor transactivational capacity is determined by both cellular and promoter context and mediated by two functionally distinct intramolecular regions. Mol Endocrinol 8:21-30
78. Norris JD, Fan D, Kerner SA, McDonnell DP 1997 Identification of a third autonomous activation domain within the human estrogen receptor. Mol Endocrinol 11:747-754
79. Picard D, Kumar V, Chambon P, Yamamoto KR 1990 Signal transduction by steroid hormones: nuclear localization is differentially regulated in estrogen and glucocorticoid receptors. Cell Regul 1:291-299
80. Scherrer LC, Picard D, Massa E, Harmon JM, Simons Jr SS, Yamamoto KR, Pratt WB 1993 Evidence that the hormone binding domain of steroid receptors confers hormonal control on chimeric proteins by determining their hormone-regulated binding to heat-shock protein 90. Biochemistry 32:5381-5386
81. Chambraud B, Berry M, Redeuilh G, Chambon P, Baulieu EE 1990 Several regions of human estrogen receptor are involved in the formation of receptor-heat shock protein 90 complexes. J Biol Chem 265:20686-20691
82. Klock G, Strahle U, Schutz G 1987 Oestrogen and glucocorticoid, responsive elements are closely related but distinct. Nature 329:734-736
83. Driscoll MD, Sathya G, Muyan M, Klinge CM, Hilf R, Bambara RA 1998 Sequence requirements for estrogen receptor binding to estrogen response elements. J Biol Chem 273:29321-29330
84. Klinge CM, Peale Jr FV, Hilf R, Bambara RA, Zain S 1992 Cooperative estrogen receptor interaction with consensus or variant estrogen responsive elements in vitro. Cancer Res 52:1073-1081
85. Klinge CM, Knox DT, Bambara RA, Zain S, Hilf R 1989 Antiestrogen(4- hydroxytamoxifen)-charged estrogen receptor binding to nuclei from normal and neoplastic rat mammary tissues is not affected by host hormonal status. J Steroid Biochem 33:335-340
86. Klinge CM, Traish AM, Bambara RA, Hilf R 1996 Dissociation of 4-hydroxytamoxifen, but not estradiol or tamoxifen aziridine, from the estrogen receptor as the receptor binds estrogen response element DNA. J Steroid Biochem Mol Biol 57:51-66
87. Klinge CM, Traish AM, Driscoll MD, Hilf R, Bambara RA 1996 Site-directed estrogen receptor antibodies stabilize 4-hydroxytamoxifen ligand, but not estradiol, and indicate ligand-specific differences in the recognition of estrogen response element DNA in vitro. Steroids 61:278-289
88. Anolik JH, Klinge CM, Bambara RA, Hilf R 1993 Differential impact of flanking sequences on estradiol- vs 4-hydroxytamoxifen-liganded estrogen receptor binding to estrogen responsive element DNA. J Steroid Biochem Mol Biol 46:713-730
89. Anolik JH, Klinge CM, Hilf R, Bambara RA 1995 Cooperative binding of estrogen receptor to DNA depends on spacing of binding sites, flanking sequence, and ligand. Biochemistry 34:2511-2520
90. Anolik JH, Klinge CM, Brolly CL, Bambara RA, Hilf R 1996 Stability of the ligand-estrogen receptor interaction depends on estrogen response element flanking sequences and cellular factors. J Steroid Biochem Mol Biol 59:413-429
91. Nardulli AM, Greene GL, Shapiro DJ 1993 Human estrogen receptor bound to an estrogen response element bends DNA. Mol Endocrinol 7:331-340
92. Potthoff SJ, Romine LE, Nardulli AM 1996 Effects of wild type and mutant estrogen receptors on DNA flexibility, DNA bending, and transcription activation. Mol Endocrinol 10:1095-1106
93. Kim J, de Haan G, Nardulli AM, Shapiro DJ 1997 Prebending the estrogen response element destabilizes binding of the estrogen receptor DNA binding domain. Mol Cell Biol 17:3173-3180
94. Nardulli AM, Grobner C, Cotter D 1995 Estrogen receptor-induced DNA bending: orientation of the bend and replacement of an estrogen response element with an intrinsic DNA bending sequence. Mol Endocrinol 9:1064-1076
95. Nardulli AM, Shapiro DJ 1992 Binding of the estrogen receptor DNA-binding domain to the estrogen response element induces DNA bending. Mol Cell Biol 12:2037-2042
96. Sabbah M, Le Ricousse S, Redeuilh G, Baulieu EE 1992 Estrogen receptor-induced bending of the Xenopus vitellogenin A2 gene hormone response element. Biochem Biophys Res Commun 185:944-952
97. Sadovsky Y, Webb P, Lopez G, Baxter JD, Fitzpatrick PM, Gizang-Ginsberg E, Cavailles V, Parker MG, Kushner PJ 1995 Transcriptional activators differ in their responses to overexpression of TATA-box-binding protein. Mol Cell Biol 15:1554-1563
98. Jacq X, Brou C, Lutz Y, Davidson I, Chambon P, Tora L 1994 Human TAFII30 is present in a distinct TFIID complex and is required for transcriptional activation by the estrogen receptor. Cell 79:107-117
99. Wu SY, Thomas MC, Hou SY, Likhite V, Chiang CM 1999 Isolation of mouse TFIID and functional characterization of TBP and TFIID in mediating estrogen receptor and chromatin transcription. J Biol Chem 274:23480-23490
100. Klein-Hitpass L, Schwerk C, Kahmann S, Vassen L 1998 Targets of activated steroid hormone receptors: basal transcription factors and receptor interacting proteins. J Mol Med 76:490-496
101. Chen D, Pace PE, Coombes RC, Ali S 1999 Phosphorylation of human estrogen receptor α by protein kinase A regulates dimerization. Mol Cell Biol 19:1002-1015
102. Aronica SM, Katzenellenbogen BS 1993 Stimulation of estrogen receptor-mediated transcription and alteration in the phosphorylation state of the rat uterine estrogen receptor by estrogen, cyclic adenosine monophosphate, and insulin-like growth factor-I. Mol Endocrinol 7:743-752
103. Gangolli EA, Conneely OM, O'Malley BW 1997 Neurotransmitters activate the human estrogen receptor in a neuroblastoma cell line. J Steroid Biochem Mol Biol 61:1-9
104. Auricchio F, Di Domenico M, Migliaccio A, Castoria G, Bilancio A 1995 The role of estradiol receptor in the proliferative activity of vanadate on MCF-7 cells. Cell Growth Differ 6:105-113
105. Bunone G, Briand PA, Miksicek RJ, Picard D 1996 Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation. EMBO J 15:2174-2183
106. Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H, Metzger D, Chambon P 1995 Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science 270:1491-1494
107. Weigel NL, Zhang Y 1998 Ligand-independent activation of steroid hormone receptors. J Mol Med 76:469-479
108. McDonnell DP, Vegeto E, O'Malley BW 1992 Identification of a negative regulatory function for steroid receptors. Proc Natl Acad Sci USA 89:10563-10567
109. Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y 1996 The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell 87:953-959
110. Voegel JJ, Heine MJ, Tini M, Vivat V, Chambon P, Gronemeyer H 1998 The coactivator TIF2 contains three nuclear receptor-binding motifs and mediates transactivation through CBP binding-dependent and -independent pathways. EMBO J 17:507-519
111. Endoh H, Maruyama K, Masuhiro Y, Kobayashi Y, Goto M, Tai H, Yanagisawa J, Metzger D, Hashimoto S, Kato S 1999 Purification and identification of p68 RNA helicase acting as a transcriptional coactivator specific for the activation function 1 of human estrogen receptor α. Mol Cell Biol 19:5363-5372
112. Onate SA, Tsai SY, Tsai MJ, O'Malley BW 1995 Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science 270:1354-1357
113. Webb P, Nguyen P, Valentine C, Lopez GN, Kwok GR, McInerney E, Katzenellenbogen BS, Enmark E, Gustafsson JA, Nilsson S, Kushner PJ 1999 The estrogen receptor enhances AP-1 activity by two distinct mechanisms with different requirements for receptor transactivation functions. Mol Endocrinol 13:1672-1685
114. Onate SA, Boonyaratanakornkit V, Spencer TE, Tsai SY, Tsai MJ, Edwards DP, O'Malley BW 1998 The steroid receptor coactivator-1 contains multiple receptor interacting and activation domains that cooperatively enhance the activation function 1 (AF1) and AF2 domains of steroid receptors. J Biol Chem 273:12101-12108
115. Weis KE, Ekena K, Thomas JA, Lazennec G, Katzenellenbogen BS 1996 Constitutively active human estrogen receptors containing amino acid substitutions for tyrosine 537 in the receptor protein. Mol Endocrinol 10:1388-1398
116. Anzick SL, Kononen J, Walker RL, Azorsa DO, Tanner MM, Guan XY, Sauter G, Kallioniemi OP, Trent JM, Meltzer PS 1997 AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science 277:965-968
117. Montano MM, Ekena K, Delage-Mourroux R, Chang W, Martini P, Katzenellenbogen BS 1999 An estrogen receptor-selective coregulator that potentiates the effectiveness of antiestrogens and represses the activity of estrogens. Proc Natl Acad Sci USA 96:6947-6952
118. Simon SL, Parkes A, Leygue E, Dotzlaw H, Snell L, Troup S, Adeyinka A, Watson PH, Murphy LC 2000 Expression of a repressor of estrogen receptor activity in human breast tumors: relationship to some known prognostic markers. Cancer Res 60:2796-2799
119. Spencer TE, Jenster G, Burcin MM, Allis CD, Zhou J, Mizzen CA, McKenna NJ, Onate SA, Tsai SY, Tsai MJ, O'Malley BW 1997 Steroid receptor coactivator-1 is a histone acetyltransferase. Nature 389:194-198
120. Henttu PM, Kalkhoven E, Parker MG 1997 AF-2 activity and recruitment of steroid receptor coactivator 1 to the estrogen receptor depend on a lysine residue conserved in nuclear receptors. Mol Cell Biol 17:1832-1839
121. Steinmetz AC, Renaud JP, Moras D 2001 Binding of ligands and activation of transcription by nuclear receptors. Annu Rev Biophys Biomol Struct 30:329-359
122. Weatherman RV, Fletterick RJ, Scanlan TS 1999 Nuclear-receptor ligands and ligand-binding domains. Annu Rev Biochem 68:559-581
123. Glass CK, Rosenfeld MG 2000 The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 14:121-141
124. Brzozowski AM, Pike AC, Dauter Z, Hubbard RE, Bonn T, Engstrom O, Ohman L, Greene GL, Gustafsson JA, Carlquist M 1997 Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 389:753-758
125. Tanenbaum DM, Wang Y, Williams SP, Sigler PB 1998 Crystallographic comparison of the estrogen and progesterone receptor's ligand binding domains. Proc Natl Acad Sci USA 95:5998-6003
126. Feng W, Ribeiro RC, Wagner RL, Nguyen H, Apriletti JW, Fletterick RJ, Baxter JD, Kushner PJ, West BL 1998 Hormone-dependent coactivator binding to a hydrophobic cleft on nuclear receptors. Science 280:1747-1749
127. Moras D, Gronemeyer H 1998 The nuclear receptor ligand-binding domain: structure and function. Curr Opin Cell Biol 10:384-391
128. Pike AC, Brzozowski AM, Hubbard RE, Bonn T, Thorsell AG, Engstrom O, Ljunggren J, Gustafsson JA, Carlquist M 1999 Structure of the ligand-binding domain of oestrogen receptor β in the presence of a partial agonist and a full antagonist. EMBO J 18:4608-4618
129. Pike AC, Brzozowski AM, Walton J, Hubbard RE, Bonn T, Gustafsson JA, Carlquist M 2000 Structural aspects of agonism and antagonism in the oestrogen receptor. Biochem Soc Trans 28:396-400
130. Pike AC, Brzozowski AM, Walton J, Hubbard RE, Thorsell AG, Li YL, Gustafsson JA, Carlquist M 2001 Structural insights into the mode of action of a pure antiestrogen. Structure (Camb) 9:145-153
131. Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA, Greene GL 1998 The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell 95:927-937
132. Shiau AK, Barstad D, Radek JT, Meyers MJ, Nettles KW, Katzenellenbogen BS, Katzenellenbogen JA, Agard DA, Greene GL 2002 Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonism. Nat Struct Biol 9:359-364
133. Smith CL, Nawaz Z, O'Malley BW 1997 Coactivator and corepressor regulation of the agonist/antagonist activity of the mixed antiestrogen, 4-hydroxytamoxifen. Mol Endocrinol 11:657-666
134. Lavinsky RM, Jepsen K, Heinzel T, Torchia J, Mullen TM, Schiff R, Del-Rio AL, Ricote M, Ngo S, Gemsch J, Hilsenbeck SG, Osborne CK, Glass CK, Rosenfeld MG, Rose DW 1998 Diverse signaling pathways modulate nuclear receptor recruitment of NCoR and SMRT complexes. Proc Natl Acad Sci USA 95:2920-2925
135. Jepsen K, Hermanson O, Onami TM, Gleiberman AS, Lunyak V, McEvilly RJ, Kurokawa R, Kumar V, Liu F, Seto E, Hedrick SM, Mandel G, Glass CK, Rose DW, Rosenfeld MG 2000 Combinatorial roles of the nuclear receptor corepressor in transcription and development. Cell 102:753-763
136. Shang Y, Hu X, DiRenzo J, Lazar MA, Brown M 2000 Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell 103:843-852
137. Zhang X, Jeyakumar M, Petukhov S, Bagchi MK 1998 A nuclear receptor corepressor modulates transcriptional activity of antagonist-occupied steroid hormone receptor. Mol Endocrinol 12:513-524
138. Jackson TA, Richer JK, Bain DL, Takimoto GS, Tung L, Horwitz KB 1997 The partial agonist activity of antagonist-occupied steroid receptors is controlled by a novel hinge domain-binding coactivator L7/SPA and the corepressors N-CoR or SMRT. Mol Endocrinol 11:693-705
139. Webb P, Valentine C, Nguyen P, Price Jr RH, Marimuthu A, West BL, Baxter JD, Kushner PJ 2003 ERβ binds N-CoR in the presence of estrogens via an LXXLL-like motif in the N-CoR C-terminus. Nucl Recept 1:4
140. Graham JD, Bain DL, Richer JK, Jackson TA, Tung L, Horwitz KB 2000 Thoughts on tamoxifen resistant breast cancer. Are coregulators the answer or just a red herring? J Steroid Biochem Mol Biol 74:255-259
141. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA 1998 Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β. Endocrinology 139:4252-4263
142. Kuiper GG, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson JA 1997 Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and β. Endocrinology 138:863-870
143. Perlmann T, Evans RM 1997 Nuclear receptors in Sicily: all in the famiglia. Cell 90:391-397
144. McInerney EM, Weis KE, Sun J, Mosselman S, Katzenellenbogen BS 1998 Transcription activation by the human estrogen receptor subtype β (ER β) studied with ER β and ER α receptor chimeras. Endocrinology 139:4513-4522
145. Hall JM, McDonnell DP 1999 The estrogen receptor β-isoform (ERβ) of the human estrogen receptor modulates ERα transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens. Endocrinology 140:5566-5578
146. Delaunay F, Pettersson K, Tujague M, Gustafsson JA 2000 Functional differences between the amino-terminal domains of estrogen receptors α and β. Mol Pharmacol 58:584-590
147. Hyder SM, Chiappetta C, Stancel GM 1999 Interaction of human estrogen receptors α and β with the same naturally occurring estrogen response elements. Biochem Pharmacol 57:597-601
148. Cowley SM, Parker MG 1999 A comparison of transcriptional activation by ER α and ER β. J Steroid Biochem Mol Biol 69:165-175
149. Paech K, Webb P, Kuiper GG, Nilsson S, Gustafsson J, Kushner PJ, Scanlan TS 1997 Differential ligand activation of estrogen receptors ERα and ERβ at AP1 sites. Science 277:1508-1510
150. Wissink S, van der Burg B, Katzenellenbogen BS, van der Saag PT 2001 Synergistic activation of the serotonin-1A receptor by nuclear factor-κB and estrogen. Mol Endocrinol 15:543-552
151. Lazennec G, Bresson D, Lucas A, Chauveau C, Vignon F 2001 ER β inhibits proliferation and invasion of breast cancer cells. Endocrinology 142:4120-4130
152. Shughrue P, Scrimo P, Lane M, Askew R, Merchenthaler I 1997 The distribution of estrogen receptor-β mRNA in forebrain regions of the estrogen receptor-α knockout mouse. Endocrinology 138: 5649-5652
153. Rosenfeld CS, Ganjam VK, Taylor JA, Yuan X, Stiehr JR, Hardy MP, Lubahn DB 1998 Transcription and translation of estrogen receptor-β in the male reproductive tract of estrogen receptor-α knock-out and wild-type mice. Endocrinology 139:2982-2987
154. Couse JF, Lindzey J, Grandien K, Gustafsson JA, Korach KS 1997 Tissue distribution and quantitative analysis of estrogen receptor-α (ERα) and estrogen receptor-β (ERβ) messenger ribonucleic acid in the wild-type and ERα-knockout mouse. Endocrinology 138:4613-4621
155. Shughrue PJ 1998 Estrogen action in the estrogen receptor α-knockout mouse: is this due to ER-β? Mol Psychiatry 3:299-302
156. Shughrue PJ, Lane MV, Merchenthaler I 1999 Biologically active estrogen receptor-β: evidence from in vivo autoradiographic studies with estrogen receptor α-knockout mice. Endocrinology 140: 2613-2620
157. Forster C, Makela S, Warri A, Kietz S, Becker D, Hultenby K, Warner M, Gustafsson JA 2002 Involvement of estrogen receptor β in terminal differentiation of mammary gland epithelium. Proc Natl Acad Sci USA 99:15578-15583
158. Russell KS, Haynes MP, Sinha D, Clerisme E, Bender JR 2000 Human vascular endothelial cells contain membrane binding sites for estradiol, which mediate rapid intracellular signaling. Proc Natl Acad Sci USA 97:5930-5935
159. Pendaries C, Darblade B, Rochaix P, Krust A, Chambon P, Korach KS, Bayard F, Arnal JF 2002 The AF-1 activation-function of ERα may be dispensable to mediate the effect of estradiol on endothelial NO production in mice. Proc Natl Acad Sci USA 99:2205-2210
160. Day JK, Besch-Williford C, McMann TR, Hufford MG, Lubahn DB, MacDonald RS 2001 Dietary genistein increased DMBA-induced mammary adenocarcinoma in wild-type, but not ER α KO, mice. Nutr Cancer 39:226-232
161. Bocchinfuso WP, Hively WP, Couse JF, Varmus HE, Korach KS 1999 A mouse mammary tumor virus-Wnt-1 transgene induces mammary gland hyperplasia and tumorigenesis in mice lacking estrogen receptor-α. Cancer Res 59:1869-1876
162. Hewitt SC, Bocchinfuso WP, Zhai J, Harrell C, Koonce L, Clark J, Myers P, Korach KS 2002 Lack of ductal development in the absence of functional estrogen receptor α delays mammary tumor formation induced by transgenic expression of ErbB2/neu. Cancer Res 62:2798-2805
163. Anderson TJ, Ferguson DJ, Raab GM 1982 Cell turnover in the
164. Dickson RB, Huff KK, Spencer EM, Lippman ME 1986 Induction of epidermal growth factor-related polypeptides by 17 β-estradiol in MCF-7 human breast cancer cells. Endocrinology 118:138-142
165. Huseby RA, Maloney TM, McGrath CM 1984 Evidence for a direct growth-stimulating effect of estradiol on human MCF-7 cells in vivo. Cancer Res 44:2654-2659
166. Mueller SO, Clark JA, Myers PH, Korach KS 2002 Mammary gland development in adult mice requires epithelial and stromal estrogen receptor α. Endocrinology 143:2357-2365
167. Allegra JC, Lippman ME, Green L, Barlock A, Simon R, Thompson EB, Huff KK, Griffin W 1979 Estrogen receptor values in patients with benign breast disease. Cancer 44:228-231
168. Ricketts D, Turnbull L, Ryall G, Bakhshi R, Rawson NS, Gazet JC, Nolan C, Coombes RC 1991 Estrogen and progesterone receptors in the normal female breast. Cancer Res 51:1817-1822
169. Petersen OW, Hoyer PE, van Deurs B 1987 Frequency and distribution of estrogen receptor-positive cells in normal, nonlactating human breast tissue. Cancer Res 47:5748-5751
170. Schmitt FC 1995 Multistep progression from an oestrogen-dependent growth towards an autonomous growth in breast carcinogenesis. Eur J Cancer 31A:2049-2052
171. Markopoulos C, Berger U, Wilson P, Gazet JC, Coombes RC 1988 Oestrogen receptor content of normal breast cells and breast carcinomas throughout the menstrual cycle. Br Med J (Clin Res Ed) 296:1349-1351
172. Williams G, Anderson E, Howell A, Watson R, Coyne J, Roberts SA, Potten CS 1991 Oral contraceptive (OCP) use increases proliferation and decreases oestrogen receptor content of epithelial cells in the normal human breast. Int J Cancer 48:206-210
173. Battersby S, Robertson BJ, Anderson TJ, King RJ, McPherson K 1992 Influence of menstrual cycle, parity and oral contraceptive use on steroid hormone receptors in normal breast. Br J Cancer 65:601-607
174. Russo J, Ao X, Grill C, Russo IH 1999 Pattern of distribution of cells positive for estrogen receptor α and progesterone receptor in relation to proliferating cells in the mammary gland. Breast Cancer Res Treat 53:217-227
175. Clarke RB, Howell A, Potten CS, Anderson E 1997 Dissociation between steroid receptor expression and cell proliferation in the human breast. Cancer Res 57:4987-4991
176. Russo J, Hu YF, Yang X, Russo IH 2000 Developmental, cellular, and molecular basis of human breast cancer. J Natl Cancer Inst Monogr 27:17-37
177. Roger P, Sahla ME, Makela S, Gustafsson JA, Baldet P, Rochefort H 2001 Decreased expression of estrogen receptor β protein in proliferative preinvasive mammary tumors. Cancer Res 61:2537-2541
178. Shaw JA, Udokang K, Mosquera JM, Chauhan H, Jones JL, Walker RA 2002 Oestrogen receptors α and β differ in normal human breast and breast carcinomas. J Pathol 198:450-457
179. Critchley HO, Henderson TA, Kelly RW, Scobie GS, Evans LR, Groome NP, Saunders PT 2002 Wild-type estrogen receptor (ERβ1) and the splice variant (ERβcx/ β2) are both expressed within the human endometrium throughout the normal menstrual cycle. J Clin Endocrinol Metab 87:5265-5273
180. Jarvinen TA, Pelto-Huikko M, Holli K, Isola J 2000 Estrogen receptor β is coexpressed with ERα and PR and associated with nodal status, grade, and proliferation rate in breast cancer. Am J Pathol 156:29-35
181. Zafrani B, Leroyer A, Fourquet A, Laurent M, Trophilme D, Validire P, Sastre-Garau X 1994 Mammographically detected ductal in situ carcinoma of the breast analyzed with a new classification. A study of 127 cases: correlation with estrogen and progesterone receptors, p53 and c-erbB-2 proteins, and proliferative activity. Semin Diagn Pathol 11:208-214
182. Chauchereau A, Savouret JF, Milgrom E 1992 Control of biosynthesis and post-transcriptional modification of the progesterone receptor. Biol Reprod 46:174-177
183. Pallis L, Wilking N, Cedermark B, Rutqvist LE, Skoog L 1992 Receptors for estrogen and progesterone in breast carcinoma in situ. Anticancer Res 12:2113-2115
184. Karayiannakis AJ, Bastounis EA, Chatzigianni EB, Makri GG, Alexiou D, Karamanakos P 1996 Immunohistochemical detection of oestrogen receptors in ductal carcinoma in situ of the breast. Eur J Surg Oncol 22:578-582
185. Albonico G, Querzoli P, Ferretti S, Magri E, Nenci I 1996 Biophenotypes of breast carcinoma in situ defined by image analysis of biological parameters. Pathol Res Pract 192:117-123
186. Giri DD, Dundas SA, Nottingham JF, Underwood JC 1989 Oestrogen receptors in benign epithelial lesions and intraduct carcinomas of the breast: an immunohistological study. Histopathology 15:575-584
187. Barnes R, Masood S 1990 Potential value of hormone receptor assay in carcinoma in situ of breast. Am J Clin Pathol 94:533-537
188. Helin HJ, Helle MJ, Kallioniemi OP, Isola JJ 1989 Immunohistochemical determination of estrogen and progesterone receptors in human breast carcinoma. Correlation with histopathology and DNA flow cytometry. Cancer 63:1761-1767
189. Poller DN, Snead DR, Roberts EC, Galea M, Bell JA, Gilmour A, Elston CW, Blamey RW, Ellis IO 1993 Oestrogen receptor expression in ductal carcinoma in situ of the breast: relationship to flow cytometric analysis of DNA and expression of the c-erbB-2 oncoprotein. Br J Cancer 68:156-161
190. Chaudhuri B, Crist KA, Mucci S, Malafa M, Chaudhuri PK 1993 Distribution of estrogen receptor in ductal carcinoma in situ of the breast. Surgery 113:134-137
191. Leal CB, Schmitt FC, Bento MJ, Maia NC, Lopes CS 1995 Ductal carcinoma in situ of the breast. Histologic categorization and its relationship to ploidy and immunohistochemical expression of hormone receptors, p53, and c-erbB-2 protein. Cancer 75:2123-2131
192. Bose S, Lesser ML, Norton L, Rosen PP 1996 Immunophenotype of intraductal carcinoma. Arch Pathol Lab Med 120:81-85
193. Roger P, Daures JP, Maudelonde T, Pignodel C, Gleizes M, Chapelle J, Marty-Double C, Baldet P, Mares P, Laffargue F, Rochefort H 2000 Dissociated overexpression of cathepsin D and estrogen receptor α in preinvasive mammary tumors. Hum Pathol 31:593-600
194. Speirs V, Kerin MJ 2000 Prognostic significance of oestrogen receptor β in breast cancer. Br J Surg 87:405-409
195. Fuqua S, Schiff R, Parra I, Moore JT, Mohsin S, Osborne CK, Clark GM, Allred DC 2003 Estrogen receptor β protein in human breast cancer: correlation with clinical tumor parameters. Cancer Res 63:2434-2439
196. Skliris GP, Carder PJ, Lansdown MR, Speirs V 2001 Immunohistochemical detection of ERβ in breast cancer: towards more detailed receptor profiling? Br J Cancer 84:1095-1098
197. Skliris GP, Munot K, Bell SM, Carder PJ, Lane S, Horgan K, Lansdown MR, Parkes AT, Hanby AM, Markham AF, Speirs V 2003 Reduced expression of oestrogen receptor β in invasive breast cancer and its re-expression using DNA methyl transferase inhibitors in a cell line model. J Pathol 201:213-220
198. Shaaban AM, O'Neill PA, Davies MP, Sibson R, West CR, Smith PH, Foster CS 2003 Declining estrogen receptor-β expression defines malignant progression of human breast neoplasia. Am J Surg Pathol 27:1502-1512
199. Speirs V 2002 Oestrogen receptor β in breast cancer: good, bad or still too early to tell? J Pathol 197:143-147
200. Knowlden JM, Gee JM, Robertson JF, Ellis IO, Nicholson RI 2000 A possible divergent role for the oestrogen receptor α and β subtypes in clinical breast cancer. Int J Cancer 89:209-212
201. Iwao K, Miyoshi Y, Egawa C, Ikeda N, Tsukamoto F, Noguchi S 2000 Quantitative analysis of estrogen receptor-α and -β messenger RNA expression in breast carcinoma by real-time polymerase chain reaction. Cancer 89:1732-1738
202. Iwao K, Miyoshi Y, Egawa C, Ikeda N, Noguchi S 2000 Quantitative analysis of estrogen receptor-β mRNA and its variants in human breast cancers. Int J Cancer 88:733-736
203. Omoto Y, Kobayashi S, Inoue S, Ogawa S, Toyama T, Yamashita H, Muramatsu M, Gustafsson JA, Iwase H 2002 Evaluation of oestrogen receptor β wild-type and variant protein expression, and relationship with clinicopathological factors in breast cancers. Eur J Cancer 38:380-386
204. Omoto Y, Inoue S, Ogawa S, Toyama T, Yamashita H, Muramatsu M, Kobayashi S, Iwase H 2001 Clinical value of the wild-type estrogen receptor β expression in breast cancer. Cancer Lett 163: 207-212
205. Mann S, Laucirica R, Carlson N, Younes PS, Ali N, Younes A, Li Y, Younes M 2001 Estrogen receptor β expression in invasive breast cancer. Hum Pathol 32:113-118
206. Miyoshi Y, Taguchi T, Gustafsson JA, Noguchi S 2001 Clinicopathological characteristics of estrogen receptor-β-positive human breast cancers. Jpn J Cancer Res 92:1057-1061
207. Jensen EV, Cheng G, Palmieri C, Saji S, Makela S, Van Noorden S, Wahlstrom T, Warner M, Coombes RC, Gustafsson JA 2001 Estrogen receptors and proliferation markers in primary and recurrent breast cancer. Proc Natl Acad Sci USA 98:15197-15202
208. Harvey JM, Clark GM, Osborne CK, Allred DC 1999 Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 17:1474-1481
209. Allred DC, Harvey JM, Berardo M, Clark GM 1998 Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155-168
210. Leygue E, Dotzlaw H, Watson PH, Murphy LC 1998 Altered estrogen receptor α and β messenger RNA expression during human breast tumorigenesis. Cancer Res 58:3197-3201
211. Brand H, Kos M, Denger S, Flouriot G, Gromoll J, Gannon F, Reid G 2002 A novel promoter is involved in the expression of estrogen receptor α in human testis and epididymis. Endocrinology 143: 3397-3404
212. Piva R, Bianchi N, Aguiari GL, Gambari R, del Senno L 1993 Sequencing of an RNA transcript of the human estrogen receptor gene: evidence for a new transcriptional event. J Steroid Biochem Mol Biol 46:531-538
213. Thompson DA, McPherson LA, Carmeci C, deConinck EC, Weigel RJ 1997 Identification of two estrogen receptor transcripts with novel 5′ exons isolated from a MCF7 cDNA library. J Steroid Biochem Mol Biol 62:143-153
214. Keaveney M, Klug J, Dawson MT, Nestor PV, Neilan JG, Forde RC, Gannon F 1991 Evidence for a previously unidentified upstream exon in the human oestrogen receptor gene. J Mol Endocrinol 6:111-115
215. Grandien K 1996 Determination of transcription start sites in the human estrogen receptor gene and identification of a novel, tissue-specific, estrogen receptor-mRNA isoform. Mol Cell Endocrinol 116:207-212
216. Flouriot G, Griffin C, Kenealy M, Sonntag-Buck V, Gannon F 1998 Differentially expressed messenger RNA isoforms of the human estrogen receptor-α gene are generated by alternative splicing and promoter usage. Mol Endocrinol 12:1939-1954
217. Kos M, Reid G, Denger S, Gannon F 2001 Minireview: genomic organization of the human ERα gene promoter region. Mol Endocrinol 15:2057-2063
218. Kos M, Denger S, Reid G, Gannon F 2002 Upstream open reading frames regulate the translation of the multiple mRNA variants of the estrogen receptor α. J Biol Chem 277:37131-37138
219. Reid G, Denger S, Kos M, Gannon F 2002 Human estrogen receptor-α: regulation by synthesis, modification and degradation. Cell Mol Life Sci 59:821-831
220. Petursdottir V, Moslemi AR, Persson M, Nordborg E, Nordborg C 2001 Estrogen receptor α in giant cell arteritis: a molecular genetic study. Clin Exp Rheumatol 19:297-302
221. Kassi EN, Vlachoyiannopoulos PG, Moutsopoulos HM, Sekeris CE, Moutsatsou P 2001 Molecular analysis of estrogen receptor α and β in lupus patients. Eur J Clin Invest 31:86-93
222. Chaidarun SS, Klibanski A, Alexander JM 1997 Tumor-specific expression of alternatively spliced estrogen receptor messenger ribonucleic acid variants in human pituitary adenomas. J Clin Endocrinol Metab 82:1058-1065
223. Pfeffer U, Fecarotta E, Vidali G 1995 Coexpression of multiple estrogen receptor variant messenger RNAs in normal and neoplastic breast tissues and in MCF-7 cells. Cancer Res 55:2158-2165
224. Rice LW, Jazaeri AA, Shupnik MA 1997 Estrogen receptor mRNA splice variants in pre- and postmenopausal human endometrium and endometrial carcinoma. Gynecol Oncol 65:149-157
225. Zhang QX, Hilsenbeck SG, Fuqua SA, Borg A 1996 Multiple splicing variants of the estrogen receptor are present in individual human breast tumors. J Steroid Biochem Mol Biol 59:251-260
226. Murphy LC, Wang M, Coutt A, Dotzlaw H 1996 Novel mutations in the estrogen receptor messenger RNA in human breast cancers. J Clin Endocrinol Metab 81:1420-1427
227. Anandappa SY, Sibson R, Platt-Higgins A, Winstanley JH, Rudland PS, Barraclough R 2000 Variant estrogen receptor α mRNAs in human breast cancer specimens. Int J Cancer 88:209-216
228. Wang Y, Miksicek RJ 1991 Identification of a dominant negative form of the human estrogen receptor. Mol Endocrinol 5:1707-1715
229. Ignar-Trowbridge DM, Pimentel M, Parker MG, McLachlan JA, Korach KS 1996 Peptide growth factor cross-talk with the estrogen receptor requires the A/B domain and occurs independently of protein kinase C or estradiol. Endocrinology 137:1735-1744
230. Madsen MW, Reiter BE, Larsen SS, Briand P, Lykkesfeldt AE 1997 Estrogen receptor messenger RNA splice variants are not involved in antiestrogen resistance in sublines of MCF-7 human breast cancer cells. Cancer Res 57:585-589
231. Leygue ER, Watson PH, Murphy LC 1996 Estrogen receptor variants in normal human mammary tissue. J Natl Cancer Inst 88:284-290
232. Daffada AA, Dowsett M 1995 Tissue-dependent expression of a novel splice variant of the human oestrogen receptor. J Steroid Biochem Mol Biol 55:413-421
233. Horvath G, Leser G, Hahlin M, Henriksson M 2000 Exon deletions and variants of human estrogen receptor mRNA in endometrial hyperplasia and adenocarcinoma. Int J Gynecol Cancer 10:128-136
234. Iwase H, Omoto Y, Iwata H, Hara Y, Ando Y, Kobayashi S 1998 Genetic and epigenetic alterations of the estrogen receptor gene and hormone independence in human breast cancer. Oncology 55(Suppl 1):11-16
235. Erenburg I, Schachter B, Mira y Lopez R, Ossowski L 1997 Loss of an estrogen receptor isoform (ERα Δ3) in breast cancer and the consequences of its reexpression: interference with estrogen-stimulated properties of malignant transformation. Mol Endocrinol 11:2004-2015
236. Miksicek RJ, Lei Y, Wang Y 1993 Exon skipping gives rise to alternatively spliced forms of the estrogen receptor in breast tumor cells. Breast Cancer Res Treat 26:163-174
237. Koehorst SG, Cox JJ, Donker GH, Lopes da Silva S, Burbach JP, Thijssen JH, Blankenstein MA 1994 Functional analysis of an alternatively spliced estrogen receptor lacking exon 4 isolated from MCF-7 breast cancer cells and meningioma tissue. Mol Cell Endocrinol 101:237-245
238. Leygue E, Huang A, Murphy LC, Watson PH 1996 Prevalence of estrogen receptor variant messenger RNAs in human breast cancer. Cancer Res 56:4324-4327
239. Fuqua SA, Fitzgerald SD, Chamness GC, Tandon AK, McDonnell DP, Nawaz Z, O'Malley BW, McGuire WL 1991 Variant human breast tumor estrogen receptor with constitutive transcriptional activity. Cancer Res 51:105-109
240. Fuqua S, Wiltschke C, Castles CG, Wolf DC, Allred DC 1995 A role for estrogen-receptor variants in endocrine resistance. Endocr Rel Cancer 2:19-25
241. Lemieux P, Fuqua S 1996 The role of the estrogen receptor in tumor progression. J Steroid Biochem Mol Biol 56:87-91
242. Rea D, Parker MG 1996 Effects of an exon 5 variant of the estrogen receptor in MCF-7 breast cancer cells. Cancer Res 56:1556-1563
243. Daffada AA, Johnston SR, Smith IE, Detre S, King N, Dowsett M 1995 Exon 5 deletion variant estrogen receptor messenger RNA expression in relation to tamoxifen resistance and progesterone receptor/pS2 status in human breast cancer. Cancer Res 55:288-293
244. Fuqua SA, Allred DC, Auchus RJ 1993 Expression of estrogen receptor variants. J Cell Biochem Suppl 17G:194-197
245. Castles CG, Fuqua SA, Klotz DM, Hill SM 1993 Expression of a constitutively active estrogen receptor variant in the estrogen receptor-negative BT-20 human breast cancer cell line. Cancer Res 53:5934-5939
246. Desai AJ, Luqmani YA, Walters JE, Coope RC, Dagg B, Gomm JJ, Pace PE, Rees CN, Thirunavukkarasu V, Shousha S, Groome NP, Coombes R, Ali S 1997 Presence of exon 5-deleted oestrogen receptor in human breast cancer: functional analysis and clinical significance. Br J Cancer 75:1173-1184
247. Zhang QX, Borg A, Fuqua SA 1993 An exon 5 deletion variant of the estrogen receptor frequently coexpressed with wild-type estrogen receptor in human breast cancer. Cancer Res 53:5882-5884
248. Pfeffer U, Fecarotta E, Arena G, Forlani A, Vidali G 1996 Alternative splicing of the estrogen receptor primary transcript normally occurs in estrogen receptor positive tissues and cell lines. J Steroid Biochem Mol Biol 56:99-105
249. Wilson KB, Evans M, Abdou NI 1996 Presence of a variant form of the estrogen receptor in peripheral blood mononuclear cells from normal individuals and lupus patients. J Reprod Immunol 31:199-208
250. Suenaga R, Evans MJ, Mitamura K, Rider V, Abdou NI 1998 Peripheral blood T cells and monocytes and B cell lines derived from patients with lupus express estrogen receptor transcripts similar to those of normal cells. J Rheumatol 25:1305-1312
251. Poola I, Speirs V 2001 Expression of alternatively spliced estrogen receptor α mRNAs is increased in breast cancer tissues. J Steroid Biochem Mol Biol 78:459-469
252. Poola I, Koduri S, Chatra S, Clarke R 2000 Identification of twenty alternatively spliced estrogen receptor α mRNAs in breast cancer cell lines and tumors using splice targeted primer approach. J Steroid Biochem Mol Biol 72:249-258
253. McGuire WL, Chamness GC, Fuqua SA 1991 Estrogen receptor variants in clinical breast cancer. Mol Endocrinol 5:1571-1577
254. Fuqua SA, Fitzgerald SD, Allred DC, Elledge RM, Nawaz Z, McDonnell DP, O'Malley BW, Greene GL, McGuire WL 1992 Inhibition of estrogen receptor action by a naturally occurring variant in human breast tumors. Cancer Res 52:483-486
255. Garcia Pedrero JM, Zuazua P, Martinez-Campa C, Lazo PS, Ramos S 2003 The naturally occurring variant of estrogen receptor (ER) ERΔE7 suppresses estrogen-dependent transcriptional activation by both wild-type ERα and ERβ. Endocrinology 144:2967-2976
256. Koehorst SG, Jacobs HM, Thijssen JH, Blankenstein MA 1993 Wild type and alternatively spliced estrogen receptor messenger RNA in human meningioma tissue and MCF7 breast cancer cells. J Steroid Biochem Mol Biol 45:227-233
257. Ye Q, Chung LW, Cinar B, Li S, Zhau HE 2000 Identification and characterization of estrogen receptor variants in prostate cancer cell lines. J Steroid Biochem Mol Biol 75:21-31
258. Pink JJ, Wu SQ, Wolf DM, Bilimoria MM, Jordan VC 1996 A novel 80 kDa human estrogen receptor containing a duplication of exons 6 and 7. Nucleic Acids Res 24:962-969
259. Pink JJ, Jordan VC 1996 Models of estrogen receptor regulation by estrogens and antiestrogens in breast cancer cell lines. Cancer Res 56:2321-2330
260. Pink JJ, Jiang SY, Fritsch M, Jordan VC 1995 An estrogen-independent MCF-7 breast cancer cell line which contains a novel 80-kilodalton estrogen receptor-related protein. Cancer Res 55:2583-2590
261. Pink JJ, Fritsch M, Bilimoria MM, Assikis VJ, Jordan VC 1997 Cloning and characterization of a 77-kDa oestrogen receptor isolated from a human breast cancer cell line. Br J Cancer 75:17-27
262. Wang M, Dotzlaw H, Fuqua SA, Murphy LC 1997 A point mutation in the human estrogen receptor gene is associated with the expression of an abnormal estrogen receptor mRNA containing a 69 novel nucleotide insertion. Breast Cancer Res Treat 44:145-151
263. Karnik PS, Kulkarni S, Liu XP, Budd GT, Bukowski RM 1994 Estrogen receptor mutations in tamoxifen-resistant breast cancer. Cancer Res 54:349-353
264. Kumar V, Green S, Staub A, Chambon P 1986 Localisation of the oestradiol-binding and putative DNA-binding domains of the human oestrogen receptor. EMBO J 5:2231-2236
265. Ali S, Metzger D, Bornert JM, Chambon P 1993 Modulation of transcriptional activation by ligand-dependent phosphorylation of the human oestrogen receptor A/B region. EMBO J 12:1153-1160
266. Huang A, Pettigrew NM, Watson PH 1996 Immunohistochemical assay for oestrogen receptors in paraffin wax sections of breast carcinoma using a new monoclonal antibody. J Pathol 180:223-227
267. Saccani Jotti G, Johnston SR, Salter J, Detre S, Dowsett M 1994 Comparison of new immunohistochemical assay for oestrogen receptor in paraffin wax embedded breast carcinoma tissue with quantitative enzyme immunoassay. J Clin Pathol 47:900-905
268. Huang A, Leygue ER, Snell L, Murphy LC, Watson PH 1997 Expression of estrogen receptor variant messenger RNAs and determination of estrogen receptor status in human breast cancer. Am J Pathol 150:1827-1833
269. Park W, Choi JJ, Hwang ES, Lee JH 1996 Identification of a variant estrogen receptor lacking exon 4 and its coexpression with wild-type estrogen receptor in ovarian carcinomas. Clin Cancer Res 2:2029-2035
270. Inoue S, Ogawa S, Horie K, Hoshino S, Goto W, Hosoi T, Tsutsumi O, Muramatsu M, Ouchi Y 2000 An estrogen receptor β isoform that lacks exon 5 has dominant negative activity on both ERα and ERβ. Biochem Biophys Res Commun 279:814-819
271. Roodi N, Bailey LR, Kao WY, Verrier CS, Yee CJ, Dupont WD, Parl FF 1995 Estrogen receptor gene analysis in estrogen receptor-positive and receptor-negative primary breast cancer. J Natl Cancer Inst 87:446-451
272. Zhang QX, Borg A, Wolf DM, Oesterreich S, Fuqua SA 1997 An estrogen receptor mutant with strong hormone-independent activity from a metastatic breast cancer. Cancer Res 57:1244-1249
273. Fuqua SA, Wiltschke C, Zhang QX, Borg A, Castles CG, Friedrichs WE, Hopp T, Hilsenbeck S, Mohsin S, O'Connell P, Allred DC 2000 A hypersensitive estrogen receptor-α mutation in premalignant breast lesions. Cancer Res 60:4026-4029
274. McGuire WL, Chamness GC, Fuqua SA 1992 Abnormal estrogen receptor in clinical breast cancer. J Steroid Biochem Mol Biol 43:243-247
275. Garcia T, Lehrer S, Bloomer WD, Schachter B 1988 A variant estrogen receptor messenger ribonucleic acid is associated with reduced levels of estrogen binding in human mammary tumors. Mol Endocrinol 2:785-791
276. Garcia T, Sanchez M, Cox JL, Shaw PA, Ross JB, Lehrer S, Schachter B 1989 Identification of a variant form of the human estrogen receptor with an amino acid replacement. Nucleic Acids Res 17:8364
277. Lehrer S, Rabin J, Stone J, Berkowitz GS 1994 Association of an estrogen receptor variant with increased height in women. Horm Metab Res 26:486-488
278. Lehrer S, Sanchez M, Song HK, Dalton J, Levine E, Savoretti P, Thung SN, Schachter B 1990 Oestrogen receptor B-region polymorphism and spontaneous abortion in women with breast cancer. Lancet 335:622-624
279. Schmutzler RK, Sanchez M, Lehrer S, Chaparro CA, Phillips C, Rabin J, Schachter B 1991 Incidence of an estrogen receptor polymorphism in breast cancer patients. Breast Cancer Res Treat 19:111-117
280. Zhang Z, Yamashita H, Toyama T, Omoto Y, Sugiura H, Hara Y, Haruki N, Kobayashi S, Iwase H 2003 Estrogen receptor α mutation (A-to-G transition at nucleotide 908) is not found in different types of breast lesions from Japanese women. Breast Cancer 10: 70-73
281. Wang C, Fu M, Angeletti RH, Siconolfi-Baez L, Reutens AT, Albanese C, Lisanti MP, Katzenellenbogen BS, Kato S, Hopp T, Fuqua SA, Lopez GN, Kushner PJ, Pestell RG 2001 Direct acetylation of the estrogen receptor α hinge region by p300 regulates transactivation and hormone sensitivity. J Biol Chem 276:18375-18383
282. Graham 2nd ML, Krett NL, Miller LA, Leslie KK, Gordon DF, Wood WM, Wei LL, Horwitz KB 1990 T47DCO cells, genetically unstable and containing estrogen receptor mutations, are a model for the progression of breast cancers to hormone resistance. Cancer Res 50:6208-6217
283. Kohler MF, Berkholz A, Risinger JI, Elbendary A, Boyd J, Berchuck A 1995 Mutational analysis of the estrogen-receptor gene in endometrial carcinoma. Obstet Gynecol 86:33-37
284. Castoria G, Migliaccio A, Green S, Di Domenico M, Chambon P, Auricchio F 1993 Properties of a purified estradiol-dependent calf uterus tyrosine kinase. Biochemistry 32:1740-1750
285. Arnold SF, Notides AC 1995 An antiestrogen: a phosphotyrosyl peptide that blocks dimerization of the human estrogen receptor. Proc Natl Acad Sci USA 92:7475-7479
286. Arnold SF, Obourn JD, Jaffe H, Notides AC 1995 Phosphorylation of the human estrogen receptor on tyrosine 537 in vivo and by src family tyrosine kinases in vitro. Mol Endocrinol 9:24-33
287. Assikis VJ, Bilimoria MM, Muenzner HD, Lurain JR, Jordan VC 1996 Mutations of the estrogen receptor in endometrial carcinoma: evidence of an association with high tumor grade. Gynecol Oncol 63:192-199
288. Malamitsi-Puchner A, Tziotis J, Evangelopoulos D, Fountas L, Vlachos G, Creatsas G, Sekeris CE, Moutsatsou P 2001 Gene analysis of the N-terminal region of the estrogen receptor α in preeclampsia. Steroids 66:695-700
289. Dotzlaw H, Alkhalaf M, Murphy LC 1992 Characterization of estrogen receptor variant mRNAs from human breast cancers. Mol Endocrinol 6:773-785
290. Iwase H, Kobayashi S, Iwata H, Yamashita T, Ito K, Toyama T, Hara Y, Greenman J, Mathew CG 1996 [Molecular analysis of the estrogen receptor (ER) gene in association with ER negativity in breast cancer]. Gan To Kagaku Ryoho 23(Suppl 1):61-65
291. Iwase H, Greenman JM, Barnes DM, Hodgson S, Bobrow L, Mathew CG 1996 Sequence variants of the estrogen receptor (ER) gene found in breast cancer patients with ER negative and progesterone receptor positive tumors. Cancer Lett 108:179-184
292. Jurada S, Marc J, Prezelj J, Kocijancic A, Komel R 2001 Codon 325 sequence polymorphism of the estrogen receptor α gene and bone mineral density in postmenopausal women. J Steroid Biochem Mol Biol 78:15-20
293. MacGregor Schafer J, Liu H, Levenson AS, Horiguchi J, Chen Z, Jordan VC 2001 Estrogen receptor α mediated induction of the transforming growth factor α gene by estradiol and 4-hydroxytamoxifen in MDA-MB-231 breast cancer cells. J Steroid Biochem Mol Biol 78:41-50
294. Lonard DM, Nawaz Z, Smith CL, O'Malley BW 2000 The 26S proteasome is required for estrogen receptor-α and coactivator turnover and for efficient estrogen receptor-α transactivation. Mol Cell 5:939-948
295. Lazennec G, Thomas JA, Katzenellenbogen BS 2001 Involvement of cyclic AMP response element binding protein (CREB) and estrogen receptor phosphorylation in the synergistic activation of the estrogen receptor by estradiol and protein kinase activators. J Steroid Biochem Mol Biol 77:193-203
296. Zajchowski DA, Webster L, Humm R, White 3rd FA, Simmons SJ, Bartholdi M 1997 Different estrogen receptor structural domains are required for estrogen- and tamoxifen-dependent anti-proliferative activity in human mammary epithelial cells expressing an exogenous estrogen receptor. J Steroid Biochem Mol Biol 62:373-383
297. Zhuang Y, Katzenellenbogen BS, Shapiro DJ 1995 Estrogen receptor mutants which do not bind 17 β-estradiol dimerize and bind to the estrogen response element in vivo. Mol Endocrinol 9:457-466
298. Wrenn CK, Katzenellenbogen BS 1993 Structure-function analysis of the hormone binding domain of the human estrogen receptor by region-specific mutagenesis and phenotypic screening in yeast. J Biol Chem 268:24089-24098
299. Kraus WL, Weis KE, Katzenellenbogen BS 1997 Determinants for the repression of estrogen receptor transcriptional activity by ligand-occupied progestin receptors. J Steroid Biochem Mol Biol 63:175-188
300. Pakdel F, Reese JC, Katzenellenbogen BS 1993 Identification of charged residues in an N-terminal portion of the hormone-binding domain of the human estrogen receptor important in transcriptional activity of the receptor. Mol Endocrinol 7:1408-1417
301. Huang HJ, Norris JD, McDonnell DP 2002 Identification of a negative regulatory surface within estrogen receptor α provides evidence in support of a role for corepressors in regulating cellular responses to agonists and antagonists. Mol Endocrinol 16:1778-1792
302. Norris JD, Fan D, Stallcup MR, McDonnell DP 1998 Enhancement of estrogen receptor transcriptional activity by the coactivator GRIP-1 highlights the role of activation function 2 in determining estrogen receptor pharmacology. J Biol Chem 273:6679-6688
303. Pakdel F, Katzenellenbogen BS 1992 Human estrogen receptor mutants with altered estrogen and antiestrogen ligand discrimination. J Biol Chem 267:3429-3437
304. Schwartz JA, Zhong L, Deighton-Collins S, Zhao C, Skafar DF 2002 Mutations targeted to a predicted helix in the extreme carboxyl-terminal region of the human estrogen receptor-α alter its response to estradiol and 4-hydroxytamoxifen. J Biol Chem 277: 13202-13209
305. Liu H, Lee ES, Deb Los Reyes A, Zapf JW, Jordan VC 2001 Silencing and reactivation of the selective estrogen receptor modulator-estrogen receptor α complex. Cancer Res 61:3632-3639
306. Karas RH, Gauer EA, Bieber HE, Baur WE, Mendelsohn ME 1998 Growth factor activation of the estrogen receptor in vascular cells occurs via a mitogen-activated protein kinase-independent pathway. J Clin Invest 101:2851-2861
307. Joel PB, Traish AM, Lannigan DA 1995 Estradiol and phorbol ester cause phosphorylation of serine 118 in the human estrogen receptor. Mol Endocrinol 9:1041-1052
308. Joel PB, Smith J, Sturgill TW, Fisher TL, Blenis J, Lannigan DA 1998 pp90rsk1 Regulates estrogen receptor-mediated transcription through phosphorylation of Ser-167. Mol Cell Biol 18:1978-1984
309. Chen D, Washbrook E, Sarwar N, Bates GJ, Pace PE, Thirunuvakkarasu V, Taylor J, Epstein RJ, Fuller-Pace FV, Egly JM, Coombes RC, Ali S 2002 Phosphorylation of human estrogen receptor α at serine 118 by two distinct signal transduction pathways revealed by phosphorylation-specific antisera. Oncogene 21: 4921-4931
310. Rogatsky I, Trowbridge JM, Garabedian MJ 1999 Potentiation of human estrogen receptor α transcriptional activation through phosphorylation of serines 104 and 106 by the cyclin A-CDK2 complex. J Biol Chem 274:22296-22302
311. Le Goff P, Montano MM, Schodin DJ, Katzenellenbogen BS 1994 Phosphorylation of the human estrogen receptor. Identification of hormone-regulated sites and examination of their influence on transcriptional activity. J Biol Chem 269:4458-4466
312. Castano E, Chen CW, Vorojeikina DP, Notides AC 1998 The role of phosphorylation in human estrogen receptor function. J Steroid Biochem Mol Biol 65:101-110
313. Lu Q, Ebling H, Mittler J, Baur WE, Karas RH 2002 MAP kinase mediates growth factor-induced nuclear translocation of estrogen receptor α. FEBS Lett 516:1-8
314. Wolf DM, Jordan VC 1994 The estrogen receptor from a tamoxifen stimulated MCF-7 tumor variant contains a point mutation in the ligand binding domain. Breast Cancer Res Treat 31:129-138
315. Wolf DM, Jordan VC 1994 Characterization of tamoxifen stimulated MCF-7 tumor variants grown in athymic mice. Breast Cancer Res Treat 31:117-127
316. Liu H, Park WC, Bentrem DJ, McKian KP, Reyes Ade L, Loweth JA, Schafer JM, Zapf JW, Jordan VC 2002 Structure-function relationships of the raloxifene-estrogen receptor-α complex for regulating transforming growth factor-α expression in breast cancer cells. J Biol Chem 277:9189-9198
317. Bentrem D, Dardes R, Liu H, MacGregor-Schafer J, Zapf J, Jordan V 2001 Molecular mechanism of action at estrogen receptor α of a new clinically relevant antiestrogen (GW7604) related to tamoxifen. Endocrinology 142:838-846
318. Catherino WH, Wolf DM, Jordan VC 1995 A naturally occurring estrogen receptor mutation results in increased estrogenicity of a tamoxifen analog. Mol Endocrinol 9:1053-1063
319. Levenson AS, Catherino WH, Jordan VC 1997 Estrogenic activity is increased for an antiestrogen by a natural mutation of the estrogen receptor. J Steroid Biochem Mol Biol 60:261-268
320. Levenson AS, Jordan VC 1998 The key to the antiestrogenic mechanism of raloxifene is amino acid 351 (aspartate) in the estrogen receptor. Cancer Res 58:1872-1875
321. Levenson AS, MacGregor Schafer JI, Bentrem DJ, Pease KM, Jordan VC 2001 Control of the estrogen-like actions of the tamoxifen-estrogen receptor complex by the surface amino acid at position 351. J Steroid Biochem Mol Biol 76:61-70
322. MacGregor Schafer J, Liu H, Bentrem DJ, Zapf JW, Jordan VC 2000 Allosteric silencing of activating function 1 in the 4-hydroxytamoxifen estrogen receptor complex is induced by substituting glycine for aspartate at amino acid 351. Cancer Res 60:5097-5105
323. Schafer JI, Liu H, Tonetti DA, Jordan VC 1999 The interaction of raloxifene and the active metabolite of the antiestrogen EM-800 (SC 5705) with the human estrogen receptor. Cancer Res 59:4308-4313
324. Yamamoto Y, Wada O, Suzawa M, Yogiashi Y, Yano T, Kato S, Yanagisawa J 2001 The tamoxifen-responsive estrogen receptor α mutant D351Y shows reduced tamoxifen-dependent interaction with corepressor complexes. J Biol Chem 276:42684-42691
325. Anghel SI, Perly V, Melancon G, Barsalou A, Chagnon S, Rosenauer A, Miller Jr WH, Mader S 2000 Aspartate 351 of estrogen receptor α is not crucial for the antagonist activity of antiestrogens. J Biol Chem 275:20867-20872
326. Webb P, Nguyen P, Valentine C, Weatherman RV, Scanlan TS, Kushner PJ 2000 An antiestrogen-responsive estrogen receptor-α mutant (D351Y) shows weak AF-2 activity in the presence of tamoxifen. J Biol Chem 275:37552-37558
327. Jiang SY, Parker CJ, Jordan VC 1993 A model to describe how a point mutation of the estrogen receptor alters the structure-function relationship of antiestrogens. Breast Cancer Res Treat 26:139-147
328. Jiang SY, Langan-Fahey SM, Stella AL, McCague R, Jordan VC 1992 Point mutation of estrogen receptor (ER) in the ligand-binding domain changes the pharmacology of antiestrogens in ER-negative breast cancer cells stably expressing complementary DNAs for ER. Mol Endocrinol 6:2167-2174
329. Tora L, Mullick A, Metzger D, Ponglikitmongkol M, Park I, Chambon P 1989 The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties. EMBO J 8:1981-1986
330. Smith CL, Conneely OM, O'Malley BW 1993 Modulation of the ligand-independent activation of the human estrogen receptor by hormone and antihormone. Proc Natl Acad Sci USA 90:6120-6124
331. Aumais JP, Lee HS, Lin R, White JH 1997 Selective interaction of hsp90 with an estrogen receptor ligand-binding domain containing a point mutation. J Biol Chem 272:12229-12235
332. Metzger D, Berry M, Ali S, Chambon P 1995 Effect of antagonists on DNA binding properties of the human estrogen receptor in vitro and in vivo. Mol Endocrinol 9:579-591
333. Reese JC, Wooge CH, Katzenellenbogen BS 1992 Identification of two cysteines closely positioned in the ligand-binding pocket of the human estrogen receptor: roles in ligand binding and transcriptional activation. Mol Endocrinol 6:2160-2166
334. Neff S, Sadowski C, Miksicek RJ 1994 Mutational analysis of cysteine residues within the hormone-binding domain of the human estrogen receptor identifies mutants that are defective in both DNA-binding and subcellular distribution. Mol Endocrinol 8:1215-1223
335. Reese JC, Katzenellenbogen BS 1991 Mutagenesis of cysteines in the hormone binding domain of the human estrogen receptor. Alterations in binding and transcriptional activation by covalently and reversibly attaching ligands. J Biol Chem 266:10880-10887
336. Ekena K, Weis KE, Katzenellenbogen JA, Katzenellenbogen BS 1996 Identification of amino acids in the hormone binding domain of the human estrogen receptor important in estrogen binding. J Biol Chem 271:20053-20059
337. Ekena K, Weis KE, Katzenellenbogen JA, Katzenellenbogen BS 1997 Different residues of the human estrogen receptor are involved in the recognition of structurally diverse estrogens and antiestrogens. J Biol Chem 272:5069-5075
338. Aliau S, Mattras H, Richard E, Borgna JL 1999 Cysteine 530 of the human estrogen receptor α is the main covalent attachment site of 11β-(aziridinylalkoxyphenyl)estradiols. Biochemistry 38:14752-14762
339. Aliau S, El Garrouj D, Yasri A, Katzenellenbogen BS, Borgna JL 1997 17 α (haloacetamidoalkyl) estradiols alkylate the human estrogen receptor at cysteine residues 417 and 530. Biochemistry 36:5861-5867
340. Carlson KE, Choi I, Gee A, Katzenellenbogen BS, Katzenellenbogen JA 1997 Altered ligand binding properties and enhanced stability of a constitutively active estrogen receptor: evidence that an open pocket conformation is required for ligand interaction. Biochemistry 36:14897-14905
341. Zhong L, Skafar DF 2002 Mutations of tyrosine 537 in the human estrogen receptor-α selectively alter the receptor's affinity for estradiol and the kinetics of the interaction. Biochemistry 41:4209-4217
342. Tremblay GB, Tremblay A, Labrie F, Giguere V 1998 Ligand-independent activation of the estrogen receptors α and β by mutations of a conserved tyrosine can be abolished by antiestrogens. Cancer Res 58:877-881
343. Skafar DF 2000 Formation of a powerful capping motif corresponding to start of "helix 12" in agonist-bound estrogen receptor-α contributes to increased constitutive activity of the protein. Cell Biochem Biophys 33:53-62
344. Arnold SF, Melamed M, Vorojeikina DP, Notides AC, Sasson S 1997 Estradiol-binding mechanism and binding capacity of the human estrogen receptor is regulated by tyrosine phosphorylation. Mol Endocrinol 11:48-53
345. Arnold SF, Vorojeikina DP, Notides AC 1995 Phosphorylation of tyrosine 537 on the human estrogen receptor is required for binding to an estrogen response element. J Biol Chem 270:30205-30212
346. Yudt MR, Vorojeikina D, Zhong L, Skafar DF, Sasson S, Gasiewicz TA, Notides AC 1999 Function of estrogen receptor tyrosine 537 in hormone binding, DNA binding, and transactivation. Biochemistry 38:14146-14156
347. Ince BA, Zhuang Y, Wrenn CK, Shapiro DJ, Katzenellenbogen BS 1993 Powerful dominant negative mutants of the human estrogen receptor. J Biol Chem 268:14026-14032
348. Montano MM, Ekena K, Krueger KD, Keller AL, Katzenellenbogen BS 1996 Human estrogen receptor ligand activity inversion mutants: receptors that interpret antiestrogens as estrogens and estrogens as antiestrogens and discriminate among different antiestrogens. Mol Endocrinol 10:230-242
349. Ince BA, Schodin DJ, Shapiro DJ, Katzenellenbogen BS 1995 Repression of endogenous estrogen receptor activity in MCF-7 human breast cancer cells by dominant negative estrogen receptors. Endocrinology 136:3194-3199
350. Lee EJ, Jakacka M, Duan WR, Chien PY, Martinson F, Gehm BD, Jameson JL 2001 Adenovirus-directed expression of dominant negative estrogen receptor induces apoptosis in breast cancer cells and regression of tumors in nude mice. Mol Med 7:773-782
351. Schodin DJ, Zhuang Y, Shapiro DJ, Katzenellenbogen BS 1995 Analysis of mechanisms that determine dominant negative estrogen receptor effectiveness. J Biol Chem 270:31163-31171
352. Hirata S, Shoda T, Kato J, Hoshi K 2001 The multiple untranslated first exons system of the human estrogen receptor β (ER β) gene. J Steroid Biochem Mol Biol 78:33-40
353. Ogawa S, Inoue S, Watanabe T, Orimo A, Hosoi T, Ouchi Y, Muramatsu M 1998 Molecular cloning and characterization of human estrogen receptor βcx: a potential inhibitor of estrogen action in human. Nucleic Acids Res 26:3505-3512
354. Omoto Y, Eguchi H, Yamamoto-Yamaguchi Y, Hayashi S 2003 Estrogen receptor (ER) β1 and ERβcx/β2 inhibit ERα function differently in breast cancer cell line MCF7. Oncogene 22:5011-5020
355. Peng B, Lu B, Leygue E, Murphy LC 2003 Putative functional characteristics of human estrogen receptor-β isoforms. J Mol Endocrinol 30:13-29
356. Saji S, Omoto Y, Shimizu C, Warner M, Hayashi Y, Horiguchi S, Watanabe T, Hayashi S, Gustafsson JA, Toi M 2002 Expression of estrogen receptor (ER) (β)cx proteininER(α)-positive breast cancer: specific correlation with progesterone receptor. Cancer Res 62: 4849-4853
357. Saji S, Omoto Y, Shimizu C, Horiguchi S, Watanabe T, Funata N, Hayash S, Gustafsson JA, Toi M 2002 Clinical impact of assay of estrogen receptor β cx in breast cancer. Breast Cancer 9:303-307
358. Poola I, Abraham J, Baldwin K 2002 Identification of ten exon deleted ERβ mRNAs in human ovary, breast, uterus and bone tissues: alternate splicing pattern of estrogen receptor β mRNA is distinct from that of estrogen receptor α. FEBS Lett 516:133-138
359. Poola I, Abraham J, Liu A 2002 Estrogen receptor β splice variant mRNAs are differentially altered during breast carcinogenesis. J Steroid Biochem Mol Biol 82:169-179
360. Bjornstrom L, Sjoberg M 2002 Mutations in the estrogen receptor DNA-binding domain discriminate between the classical mechanism of action and cross-talk with Stat5b and activating protein 1 (AP-1). J Biol Chem 277:48479-48483
361. Vladusic EA, Hornby AE, Guerra-Vladusic FK, Lupu R 1998 Expression of estrogen receptor β messenger RNA variant in breast cancer. Cancer Res 58:210-214
362. Lu B, Leygue E, Dotzlaw H, Murphy LJ, Murphy LC, Watson PH 1998 Estrogen receptor-β mRNA variants in human and murine tissues. Mol Cell Endocrinol 138:199-203
363. Rosenkranz K, Hinney A, Ziegler A, Hermann H, Fichter M, Mayer H, Siegfried W, Young JK, Remschmidt H, Hebebrand J 1998 Systematic mutation screening of the estrogen receptor β gene in probands of different weight extremes: identification of several genetic variants. J Clin Endocrinol Metab 83:4524-4527
364. Arko B, Prezelj J, Komel R, Kocijancic A, Marc J 2002 No major effect of estrogen receptor β gene RsaI polymorphism on bone mineral density and response to alendronate therapy in postmenopausal osteoporosis. J Steroid Biochem Mol Biol 81:147-152
365. Murphy LC, Dotzlaw H, Leygue E, Coutts A, Watson P 1998 The pathophysiological role of estrogen receptor variants in human breast cancer. J Steroid Biochem Mol Biol 65:175-180
366. Fuqua S, Hopp T, Van M, Osborne CK, O'Connell P, Allred DC, An estrogen receptor a mutation that predicts metastatic breast cancer clinical behavior. 9th SPORE Investigators Workshop, 2001, p 174
367. Poola I, Clarke R, DeWitty R, Leffall LD 2002 Functionally active estrogen receptor isoform profiles in the breast tumors of African American women are different from the profiles in breast tumors of Caucasian women. Cancer 94:615-623
368. Jazaeri O, Shupnik MA, Jazaeri AA, Rice LW 1999 Expression of estrogen receptor α mRNA and protein variants in human endometrial carcinoma. Gynecol Oncol 74:38-47
369. Hu C, Hyder SM, Needleman DS, Baker VV 1996 Expression of estrogen receptor variants in normal and neoplastic human uterus. Mol Cell Endocrinol 118:173-179
370. Omoto Y, Iwase H, Iwata H, Hara Y, Toyama T, Ando Y, Kobayashi S 2000 Expression of estrogen receptor α exon 5 and 7 deletion variant in human breast cancers. Breast Cancer 7:27-31
371. Leslie KK, Tasset DM, Horwitz KB 1992 Functional analysis of a mutant estrogen receptor isolated from T47Dco breast cancer cells. Am J Obstet Gynecol 166:1053-1061
372. Lau KM, Mok SC, Ho SM 1999 Expression of human estrogen receptor-α and -β, progesterone receptor, and androgen receptor mRNA in normal and malignant ovarian epithelial cells. Proc Natl Acad Sci USA 96:5722-5727
373. Feng J, Yan J, Michaud S, Craddock N, Jones IR, Cook Jr EH, Goldman D, Heston LL, Peltonen L, Delisi LE, Sommer SS 2001 Scanning of estrogen receptor α (ERα) and thyroid hormone receptor α (TRα) genes in patients with psychiatric diseases: four missense mutations identified in ERα gene. Am J Med Genet 105: 369-374
374. Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, Williams TC, Lubahn DB, Korach KS 1994 Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 331:1056-1061
375. Zelada-Hedman M, Borresen-Dale AL, Lindblom A 1997 Screening of 229 family cancer patients for a germline estrogen receptor gene (ESR) base mutation. Hum Mutat 9:289
376. England GM, Bilimoria MM, Chen Z, Assikis VJ, Muenzner HD, Jordan VC 1998 Characterization of a point mutation in the hormone binding domain of the estrogen receptor from a breast tumor. Int J Oncol 12:981-986
377. Schlegel A, Wang C, Katzenellenbogen BS, Pestell RG, Lisanti MP 1999 Caveolin-1 potentiates estrogen receptor α (ERα) signaling. Caveolin-1 drives ligand-independent nuclear translocation and activation of ERα. J Biol Chem 274:33551-33556
378. Clark DE, Poteet-Smith CE, Smith JA, Lannigan DA 2001 Rsk2 allosterically activates estrogen receptor α by docking to the hormone-binding domain. EMBO J 20:3484-3494
379. Sun M, Paciga JE, Feldman RI, Yuan Z, Coppola D, Lu YY, Shelley SA, Nicosia SV, Cheng JQ 2001 Phosphatidylinositol-3-OH kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor α (ERα) via interaction between ERα and PI3K. Cancer Res 61:5985-5991
380. Mishra SK, Mazumdar A, Vadlamudi RK, Li F, Wang RA, Yu W, Jordan VC, Santen RJ, Kumar R 2003 MICoA, a novel metastasis-associated protein 1 (MTA1) interacting protein coactivator, regulates estrogen receptor-α transactivation functions. J Biol Chem 278:19209-19219
381. Wang RA, Mazumdar A, Vadlamudi RK, Kumar R 2002 P21-activated kinase-1 phosphorylates and transactivates estrogen receptor-α and promotes hyperplasia in mammary epithelium. EMBO J 21:5437-5447
382. Lee H, Bai W 2002 Regulation of estrogen receptor nuclear export by ligand-induced and p38-mediated receptor phosphorylation. Mol Cell Biol 22:5835-5845
383. Ekena K, Katzenellenbogen JA, Katzenellenbogen BS 1998 Determinants of ligand specificity of estrogen receptor-α: estrogen versus androgen discrimination. J Biol Chem 273:693-699
384. Chen S, Zhou D, Yang C, Sherman M 2001 Molecular basis for the constitutive activity of estrogen-related receptor α-1. J Biol Chem 276:28465-28470
385. Schreurs RH, Quaedackers ME, Seinen W, van der Burg B 2002 Transcriptional activation of estrogen receptor ERα and ERβ by polycyclic musks is cell type dependent. Toxicol Appl Pharmacol 183:1-9
386. Webb P, Nguyen P, Kushner PJ 2003 Differential SERM effects on corepressor binding dictate ERα activity in vivo. J Biol Chem 278: 6912-6920
387. McInerney EM, Ince BA, Shapiro DJ, Katzenellenbogen BS 1996 A transcriptionally active estrogen receptor mutant is a novel type of dominant negative inhibitor of estrogen action. Mol Endocrinol 10:1519-1526
388. Reese JC, Katzenellenbogen BS 1992 Examination of the DNA-binding ability of estrogen receptor in whole cells: implications for hormone-independent transactivation and the actions of antiestrogens. Mol Cell Biol 12:4531-4538
389. Stoica A, Katzenellenbogen BS, Martin MB 2000 Activation of estrogen receptor-α by the heavy metal cadmium. Mol Endocrinol 14:545-553
390. Stoica A, Pentecost E, Martin MB 2000 Effects of arsenite on estrogen receptor-α expression and activity in MCF-7 breast cancer cells. Endocrinology 141:3595-3602
391. Stoica A, Pentecost E, Martin MB 2000 Effects of selenite on estrogen receptor-α expression and activity in MCF-7 breast cancer cells. J Cell Biochem 79:282-292
392. Bush SM, Folta S, Lannigan DA 1996 Use of the yeast one-hybrid system to screen for mutations in the ligand-binding domain of the estrogen receptor. Steroids 61:102-109
393. Eng FC, Lee HS, Ferrara J, Willson TM, White JH 1997 Probing the structure and function of the estrogen receptor ligand binding domain by analysis of mutants with altered transactivation characteristics. Mol Cell Biol 17:4644-4653
394. Rosenauer A, Nervi C, Davison K, Lamph WW, Mader S, Miller Jr WH 1998 Estrogen receptor expression activates the transcriptional and growth-inhibitory response to retinoids without enhanced retinoic acid receptor α expression. Cancer Res 58:5110-5116
395. Jiang SY, Jordan VC 1992 Growth regulation of estrogen receptor-negative breast cancer cells transfected with complementary DNAs for estrogen receptor. J Natl Cancer Inst 84:580-591
396. Aliau S, Mattras H, Richard E, Bonnafous JC, Borgna JL 2002 Differential interactions of estrogens and antiestrogens at the 17 β-hydroxyl or counterpart hydroxyl with histidine 524 of the human estrogen receptor α. Biochemistry 41:7979-7988
397. Preisler-Mashek MT, Solodin N, Stark BL, Tyriver MK, Alarid ET 2002 Ligand-specific regulation of proteasome-mediated proteolysis of estrogen receptor-α. Am J Physiol Endocrinol Metab 282: E891-E898
398. Whelan J, Miller N 1996 Generation of estrogen receptor mutants with altered ligand specificity for use in establishing a regulatable gene expression system. J Steroid Biochem Mol Biol 58:3-12
399. Scarlata S, Miksicek R 1995 Binding properties of coumestrol to expressed human estrogen receptor. Mol Cell Endocrinol 115:65-72
400. Zhao C, Koide A, Abrams J, Deighton-Collins S, Martinez A, Schwartz JA, Koide S, Skafar DF 2003 Mutation of Leu-536 in human estrogen receptor-α alters the coupling between ligand binding, transcription activation, and receptor conformation. J Biol Chem 278:27278-27286
401. Eng FC, Barsalou A, Akutsu N, Mercier I, Zechel C, Mader S, White JH 1998 Different classes of coactivators recognize distinct but overlapping binding sites on the estrogen receptor ligand binding domain. J Biol Chem 273:28371-28377
402. Pearce ST, Liu H, Jordan VC 2003 Modulation of estrogen receptor a function and stability by tamoxifen and a critical amino acid (Asp-538) in helix 12. J Biol Chem 278:7630-7638
403. Saville B, Poukka H, Wormke M, Janne OA, Palvimo JJ, Stoner M, Samudio I, Safe S 2002 Cooperative coactivation of estrogen receptor α in ZR-75 human breast cancer cells by SNURF and TATA-binding protein. J Biol Chem 277:2485-2497
404. Webb P, Nguyen P, Shinsako J, Anderson C, Feng W, Nguyen MP, Chen D, Huang SM, Subramanian S, McKinerney E, Katzenellenbogen BS, Stallcup MR, Kushner PJ 1998 Estrogen receptor activation function 1 works by binding p160 coactivator proteins. Mol Endocrinol 12:1605-1618
405. Kraus WL, Weis KE, Katzenellenbogen BS 1995 Inhibitory crosstalk between steroid hormone receptors: differential targeting of estrogen receptor in the repression of its transcriptional activity by agonist- and antagonist-occupied progestin receptors. Mol Cell Biol 15:1847-1857
406. Kato K, Horiuchi S, Takahashi A, Ueoka Y, Arima T, Matsuda T, Kato H, Nishida Ji J, Nakabeppu Y, Wake N 2002 Contribution of estrogen receptor α to oncogenic K-Ras-mediated NIH3T3 cell transformation and its implication for escape from senescence by modulating the p53 pathway. J Biol Chem 277:11217-11224
407. Fujimoto J, Sun WS, Misao R, Sakaguchi H, Aoki I, Toyoki H, Tamaya T 2003 Expression of estrogen receptor β exon-deleted variant mRNAs in ovary and uterine endometrium. J Steroid Biochem Mol Biol 84:133-140