Adaptive hypersensitivity to estrogen: Mechanism for superiority of aromatase inhibitors over selective estrogen receptor modulators for breast cancer treatment and prevention

Endocrine-Related Cancer

Volumn 10, Issue 2, 2003, Pages 111-130

  Santen, R J ^a   Song, R X ^a   Zhang, Z ^a   Kumar, R ^d   Jeng, M H ^b   Masamura, S ^c   Yue, W ^a   Berstein, L ^a  

^a UNIVERSITY OF VIRGINIA HEALTH SYSTEM   (United States)

^b INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c TOKYO DENTAL COLLEGE   (Japan)

^d UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADAPTOR PROTEIN; AROMATASE INHIBITOR; ESTROGEN; ESTROGEN RECEPTOR; ESTROGEN RECEPTOR ALPHA; GENE PRODUCT; GROWTH FACTOR; GROWTH FACTOR RECEPTOR BOUND PROTEIN 2; MITOGEN ACTIVATED PROTEIN KINASE; MYC PROTEIN; PROGESTERONE RECEPTOR; PROTEIN C MYB; PROTEIN PS2; PROTEIN SHC; SELECTIVE ESTROGEN RECEPTOR MODULATOR; SOS PROTEIN; TAMOXIFEN;

ADAPTIVE HYPERSENSITIVITY; BREAST CANCER; BREAST CARCINOGENESIS; CANCER PREVENTION; CELL MEMBRANE; CELL NUCLEUS; CELL PROLIFERATION; CLINICAL PATHWAY; CLINICAL TRIAL; CONCENTRATION RESPONSE; CONFERENCE PAPER; DRUG MECHANISM; ENZYME ACTIVATION; ESTROGEN ACTIVITY; GENETIC TRANSFECTION; GENOTOXICITY; HORMONAL REGULATION; HORMONE SENSITIVITY; HUMAN; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; ONCOGENE C MYB; PROTEIN PHOSPHORYLATION; REPORTER GENE; SIGNAL TRANSDUCTION; TIME SERIES ANALYSIS; TRANSCRIPTION REGULATION; TUMOR CELL LINE;

ADAPTATION, PHYSIOLOGICAL; AROMATASE INHIBITORS; BREAST NEOPLASMS; CELL DIVISION; DRUG HYPERSENSITIVITY; ENZYME INHIBITORS; ESTROGENS; FEMALE; HUMANS; RECEPTORS, ESTROGEN; SELECTIVE ESTROGEN RECEPTOR MODULATORS; SIGNAL TRANSDUCTION;

EID: 0038613843     PISSN: 13510088     EISSN: None     Source Type: Journal    
DOI: 10.1677/erc.0.0100111     Document Type: Conference Paper

References (88)

1. Adam L, Vadlamudi R, Kondapaka SB, Chernoff J, Mendelsohn J & Kumar R 1998 Heregulin regulates cytoskeletal reorganization and cell migration through the p21-activated kinase-1 via phosphatidylinositol-3 kinase. Journal of Biological Chemistry 273 28238-28246.
2. ATAC Trialists' Group 2002 Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 359 2131-2139.
3. Badawi AF, Devanesan PD, Edney JA, West WW, Higginbotham S, Rogan EG & Cavalieri EL 2001 Estrogen metabolites and conjugates: biomarkers of susceptibility to human breast cancer. Proceedings of the American Association of Cancer Research 42 664.
4. Berstein LM, Zheng H, Yue W, Wang J-P, Lykkesfeldt AE, Naftolin F, Harada N, Shanabrough M & Santen RJ 2003 New approaches to the understanding of tamoxifen action and resistance. Endocrine-Related Cancer 10 267-277.
5. Blenis J 1993 Signal transduction via the MAP kinases: proceed at your own RSK. PNAS 90 5889-5892.
6. 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 aloha. Cancer Research 1869-1876.
7. Boney CM, Gruppuso PA, Faris RA & Frackelton AR Jr 2000 The critical role of Shc in insulin-like growth factor-l-mediated mitogenesis and differentiation in 3T3-L1 preadipocytes. Molecular Endocrinology 14 805-813.
8. Bonneterre J, Thurlimann B, Robertson JF, Krzakowski M, Mauriac L, Koralewski P, Vergote I, Webster A, Steinberg M & von Euler M 2000 Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the tamoxifen or arimidex randomized group efficacy and tolerability study [In Process Citation]. Journal of Clinical Oncology 18 3748-3757.
9. Buzdar A 2000 An overview of the use of non-steroidal aromatase inhibitors in the treatment of breast cancer [In Process Citation]. European Journal of Cancer 36 (Suppl 4) 82-84.
10. Buzdar A for the ATAC Trialists Group. The ATAC ('Arimadex', Tamofixen, Alone and in Combination) Trial in postmenopausal Women with Early Breast Cancer-Updated Efficacy Results Based on a Median Follow-up of 47 months. Twenty-fifth Annual San Antonio Breast Cancer Symposium, December 10-13, 2002.
11. Buzdar A 2002 Four year followup of ATAC Trial. Breast Cancer Research and Treatment (In Press).
12. Cavalieri E, Frenkel K, Liehr JG, Rogan E & Roy D 2000 Estrogens as endogenous genotoxic agents - DNA adducts and mutations. Journal of the National Cancer Institute. Monographs 27 75-93.
13. Chakravarti D, Mailander P, Cavalieri E & Rogan EG 2000 Evidence that error prone DNA repair converts dibenzo(a.l)pyrene-induced depurinating lesions into mutations; formation, clonal proliferation, and regression of initiated cells carrying H-ras oncogene mutations in early preneoplasia. Mutation Research 456 17-32.
14. Clarke R, Brunner N, Katz D, Glanz P, Dickson RB, Lippman ME & Kern FG 1989 The effects of a constitutive expression of transforming growth factor-alpha on the growth of MCF-7 human breast cancer cells in vitro and in vivo. Molecular Endocrinology 3 372-380.
15. Collins P & Webb C 1999 Estrogen hits the surface. Nature Medicine 5 1130-1131.
16. Costa LA, Kopreski MS, Demers LM, Chinchilli VM, Santen RJ, Harvey HA & Lipton A 1999 Effect of the potent aromatase inhibitor fadrozole hydrochloride (CGS 16949A) in postmenopausal women with breast carcinoma. Cancer 85 100-103.
17. Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, Norton L, Nickelsen T, Bjarnason NH, Morrow M, Lippman ME, Black D, Glusman JE, Costa A & Jordan VC 1999 The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. Journal of the American Medical Association 281 2189-2197.
18. Dickson RB & Lippman ME 2001 Oncogenes, suppressor genes, and signal transduction. In Diseases of the Breast, edn 2, pp 281-302. Eds JR Harris, ME Lippman, M Morrow & CK Osborne. Philadelphia, PA: Lippincott, Williams & Wilkins.
19. Dickson RB, Bates SE, McManaway ME & Lippman ME 1986 Characterization of estrogen responsive transforming activity in human breast cancer cell lines. Cancer Research 46 1707-1713.
20. Dikic I, Batzer AG, Blaikie P, Obermeier A, Ullrich A, Schlessinger J & Margolis B 1995 Shc binding to nerve growth factor receptor is mediated by the phosphotyrosine interaction domain. Journal of Biological Chemistry 270 15125-15129.
21. Dixon JM, Anderson T, Miller WR. Phase IIb study of neoadjuvant exemestane (EXE) in locally advanced breast cancer. Proceedings of ASCO Vol 20: abstract 1908, page 40b, Thirty seventh annual meeting of the American Society of Clinical Oncology May 12-15, 2001, San Francisco, California.
22. Dixon JM, Love CD, Renshaw L, Bellamy C, Cameron DA, Miller WR & Leonard RC 1999 Lessons from the use of aromatase inhibitors in the neoadjuvant setting. Endocrine-Related Cancer 6 227-230.
23. Dixon JM, Renshaw L, Bellamy C, Stuart M, Hoctin-Boes G & Miller WR 2000 The effects of neoadjuvant anastrozole (Arimidex) on tumor volume in postmenopausal women with breast cancer: a randomized, double-blind, single-center study [In Process Citation]. Clinical Cancer Research 6 2229-2235.
24. Dixon JM, Grattage L, Renshaw L & Miller W R 2001 Exemestane as neoadjuvant treatment for locally advanced breast cancer: endocrinologic and clinical endpoints. Abstracts, Poster Session I, 53.
25. Duffy SRG, Jackson TL on behlaf of the ATAC Trialist' Group. The ATAC ('Arimadex', tamofixen, alone and in combination) early breast cancer (EBC) trial in postmenopausal (PM) patients: endometrical subprotocol results Proceedings of ASCO Vol 21 abstract 158, page 156. Thirty-eighth annual meeting of the American Society of Clinicial Oncology May 18-21, 2002, Orlando, Florida.
26. Duan R, Xie W, Burghardt RC & Safe S 2001 Estrogen receptor-mediated activation of the serum response element in MCF-7 cells through MAPK-dependent phosphorylation of Elk-1. Journal of Biological Chemistry 276 11590-11598.
27. Ellis MJ, Coop A, Singh B, Mauriac L, Llombert-Cussac A, Janicke F, Miller WR, Evans DB, Dugan M, Brady C, Quebe-Fehling E & Borgs M. Letrozole is more effective neoadjuvant endocrine therapy than tamofixen for ErbB-1 and/or ErbB-2 positive, estrogen receptor positive primary breast cancer; evidence from a phase III randomized trial. Journal of Clinical Oncology 19 3808-3816 2001.
28. Feigelson HS, Ross RK, Yu MC, Coetzee GA, Reichardt JK & Henderson BE 1996 Genetic susceptibility to cancer from exogenous and endogenous exposures. Journal of Cellular Biochemistry 25 (Suppl) 15-22.
29. Fisher B & Redmond C 1991 New perspective on cancer of the contralateral breast: a marker for assessing tamoxifen as a preventive agent. Journal of the National Cancer Institute 83 1278-1280.
30. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L & Wolmark N 1998 Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. Journal of the National Cancer Institute 90 1371-1388.
31. Geisler J, Hayes B, Anker G, Dowsett M & Lonning PE 2002 Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross over study. Journal of Clinical Oncology 20 751-757.
32. Gottardis MM, Jiang SY, Jeng MH & Jordan VC 1989 Inhibition of tamoxifen-stimulated growth of an MCF-7 tumor variant in athymic mice by novel steroidal antiestrogens. Cancer Research 49 4090-4093.
33. Henderson BE & Feigelson HS 2000 Hormonal carcinogenesis. Carcinogenesis 21 427-433.
34. Herman ME & Katzenellenbogen BS 1994 Alterations in transforming growth factor-alpha and -beta production and cell responsiveness during the progression of MCF-7 human breast cancer cells to estrogen-autonomous growth. Cancer Research 54 5867-5874.
35. Ishikawa T, Takano K, Yasufuku-Takano J, Fujita T, Igarashi T, Miura M & Hata K 2001 Estrogenic impurities in labware. Nature Biotechnology 19 812.
36. Jackson TL & Duffy SRG 2001 The ATAC ('Arimidex', Tamoxifen, Alone or in Combinations) trial: the effectiveness of transvaginal ultrasonography and diagnostic hysteroscopy in the prediction of endometrial abnormalities in asymptomatic postmenopausal women. Abstracts, Poster Session II, 63.
37. Jeng MH, Shupnik MA, Bender TP, Westin EH, Bandyopadhyay D, Kumar R, Masamura S & Santen RJ 1998 Estrogen receptor expression and function in long-term estrogen-deprived human breast cancer cells. Endocrinology 139 4164-4174.
38. Jeng MH, Yue W, Eischeid A, Wang JP & Santen RJ 2000 Role of MAP kinase in the enhanced cell proliferation of long term estrogen deprived human breast cancer cells. Breast Cancer Research and Treatment 62 167-175.
39. Joel PB, Smith J, Sturgill TW, Fisher TL, Blenis J & Lannigan DA 1998 Rskl regulates estrogen receptor-mediated transcription through phosphorylation of Ser-167. Molecular and Cellular Biology 18 1978-1984.
40. Jordan VC, MacGregor JI & Tonetti DA 1997 Tamoxifen: from breast cancer therapy to the design of a postmenopausal prevention maintenance therapy. Clinical Oncology (Royal College of Radiologists) 9 390-394.
41. Kato S, Masuhiro Y, Watanabe M, Kobayashi Y, Takeyama KI, Endoh H & Yanagisawa J 2000 Molecular mechanism of a cross-talk between oestrogen and growth factor signalling pathways. Genes to Cells 5 593-601.
42. Katzenellenbogen BS, Kendra KL, Norman MJ & Berthois Y 1987 Proliferation, hormonal responsiveness, and estrogen receptor content of MCF-7 human breast cancer cells grown in the short-term and long-term absence of estrogens. Cancer Research 47 4355-4360.
43. Kelly MJ, Lagrange AH, Wagner EJ & Ronnekleiv OK 1999 Rapid effects of estrogen to modulate G protein-coupled receptors via activation of protein kinase A and protein kinase C pathways. Steroids 64 64-75.
44. Klein KO, Demers LM, Santner SJ, Baron J, Cutler GB Jr & Santen RJ 1995 Use of ultrasensitive recombinant cell bioassay to measure estrogen levels in women with breast cancer receiving the aromatase inhibitor, letrozole. Journal of Clinical Endocrinology and Metabolism 80 2658-2660.
45. Kong LY, Szaniszlo P, Albrecht T & Liehr JG 2000 Frequency and molecular analysis of hprt mutations induced by estradiol in Chinese hamster V79 cells. International Journal of Oncology 17 1141-1149.
46. Liu SC, Sanfilippo B, Perroteau I, Derynck R, Salomon DS & Kidwell WR 1987 Expression of transforming growth factor alpha (TGF alpha) in differentiated rat mammary tumors: estrogen induction of TGF alpha production. Molecular Endocrinology 1 683-692.
47. Masamura S, Santner SJ, Heitjan DF & Santen RJ 1995 Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells. Journal of Clinical Endocrinology and Metabolism 80 2918-2925.
48. Masamura S, Santner SJ & Santen RJ 1996 Evidence of in situ estrogen synthesis in nitrosomethylurea-induced rat mammary tumors via the enzyme estrone sulfatase. Journal of Steroid Biochemistry and Molecular Biology 58 425-429.
49. Masamura S, Santner SJ, Gimotty P, George J & Santen RJ 1997 Mechanism for maintenance of high breast tumor estradiol concentrations in the absence of ovarian function: role of very high affinity tissue uptake. Breast Cancer Research and Treatment 42 215-226.
50. Migliaccio A, Di Domenico M, Castoria G, de Falco A, Bontempo P, Nola E & Auricchio F 1996 Tyrosine kinase/p21ras/MAP-kinase pathway activation by estradiol-receptor complex in MCF-7 cells. EMBO Journal 15 1292-1300.
51. Migliaccio A, Piccolo D, Castoria G, Di Domenico M, Bilancio A, Lombardi M, Gong W, Beato M & Auricchio F 1998 Activation of the Src/p21ras/Erk pathway by progesterone receptor via cross-talk with estrogen receptor. EMBO Journal 17 2008-2018.
52. Milla-Santos A, Milla L, Rallo L & Solano V 2000 Anastrozole vs tamoxifen in hormonodependent advanced breast cancer, a phase II randomized trial. Abstracts, Twenty-third annual San Antonio breast cancer symposium, December 6-9 2000, San Antonio, Texas, USA.
53. Mouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Janicke F, Pluzanska A, Dank M & Becquart D 2001 Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. Journal of Clinical Oncology 19 2596-2606.
54. Nabholtz JM, Buzdar A, Pollak M, Harwin W, Burton G, Mangalik A, Steinberg M, Webster A & von Euler M 2000 Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a north American multicenter randomized trial [In Process Citation]. Journal of Clinical Oncology 18 3758-3767.
55. Nass SJ & Dickson RB 1997 Defining a role for c-Myc in breast tumorigenesis. Breast Cancer Research and Treatment 44 1-22.
56. Osborne CK & Fuqua SA 1994 Mechanisms of tamoxifen resistance. Breast Cancer Research and Treatment 32 49-55.
57. Osborne CK, Hamilton B, Titus G & Livingston RB 1980 Epidermal growth factor stimulation of human breast cancer cells in culture. Cancer Research 40 2361-2366.
58. Paridaens R, Dirix L, Beex L, Nooij MN, Cufer T, Lohrisch C, Biganzoli L, Van Hoorebeeck I, Duchateau L, Lobelle JP & Piccart M. Promising results with Exemestane in the first line treatment of metastatic breast cancer. A randomized Phase II EORTC trial with a tamofixen control Clinical Breast Cancer 1 S19-21 2000.
59. Paridaens R, Dirix L, Lohrisch C, Beex L, Nooij M, Cameron D, Biganzol L, Cufer T, Yague C, Lobelle JP & Piccart M 2001 Promising activity and safety of exemestane as first-line hormonal therapy in metastatic breast cancer patients: final results of an EORTC randomised phase II trial. Abstracts, Poster Session I, 52.
60. Pelicci G, Lanfrancone L, Salcini AE, Romano A, Mele S, Grazia BM, Segatto O, Di Fiore PP & Pelicci PG 1995 Constitutive phosphorylafion of Shc proteins in human tumors. Oncogene 11 899-907.
61. Pelicci G, Dente L, De Giuseppe A, Verducci-Galletti B, Giuli S, Mele S, Vetriani C, Giorgio M, Pandolfi PP, Cesareni G & Pelicci PG 1996 A family of Shc related proteins with conserved PTB, CH1 and SH2 regions. Oncogene 13 633-641.
62. Preston-Martin S, Pike MC, Ross RK, Jones PA & Henderson BE 1990 Increased cell division as a cause of human cancer. Cancer Research 50 7415-7421.
63. Roberson MS, Misra-Press A, Laurance ME, Stork PJ & Maurer RA 1995 A role for mitogen-activated protein kinase in mediating activation of the glycoprotein hormone alpha-subunit promoter by gonadotropin-releasing hormone. Molecular and Cellular Biology 15 3531-3539.
64. Rogan EL 2003 Measurement of genotoxic metabolites in human breast tissue. Carcinogenesis (In Press).
65. Russo J, Hu YF, Tahin Q, Mihaila D, Slater C, Lareef MH & Russo IH 2001 Carcinogenicity of estrogens in human breast epithelial cells. APMIS Supplementum 103 S95-S108; discussion S109-S111.
66. Santen RJ 1996 Long-term tamoxifen therapy: can an antagonist become an agonist? Journal of Clinical Endocrinology and Metabolism 81 2027-2029.
67. Santen RJ 2002 To block estrogen's synthesis or action: that is the question. Journal of Clinical Endocrinology and Metabolism 87 3007-3012.
68. Santen RJ & Harvey HA 1999 Use of aromatase inhibitors in breast carcinoma. Endocrine-Related Cancer 6 75-92.
69. Santen RJ, Manni A, Harvey H & Redmond C 1990 Endocrine treatment of breast cancer in women. Endocrine Reviews 11 221-265.
70. Sato K, Kimoto M, Kakumoto M, Horiuchi D, Iwasaki T, Tokmakov AA & Fukami Y 2000 Adaptor protein Shc undergoes translocation and mediates up-regulation of the tyrosine kinase c-Src in EGF-stimulated A431 cells. Genes to Cells 5 749-764.
71. Shim WS, Conaway M, Masamura S, Yue W, Wang JP & Santen RJ 2000 Estradiol hypersensitivity and MAP kinase expression in long term estrogen deprived human breast cancer cells in vivo. Endocrinology 141 396-405.
72. Smilenov LB, Mikhailov A, Pelham RJ, Marcantonio EE & Gundersen GG 1999 Focal adhesion motility revealed in stationary fibroblasts. Science 286 1172-1174.
73. Song R-X, Zhang Z & Santen RJ 2002a Membrane targeted ER alpha mediates the effects of 17-beta-estradiol on MAPK activation and cell proliferation. Proceedings of the 84th Annual Meeting of the Endocrine Society, San Francisco, California, 101-abstract #OR 27-N-101 June 19-22.
74. Song R-X, McPherson RA, Adam L, Bao Y, Shupnik M, Kumar R & Santen RJ 2002b Linkage of rapid estrogen action to MAPK activation by ERalpha-Shc association and Shc pathway activation. Molecular Endocrinology 16 116-127.
75. Stampfer M, Hallowes RC & Hackett AJ 1980 Growth of normal human mammary cells in culture. In Vitro 16 415-425.
76. Stefano GB, Prevot V, Beauvillain JC, Cadet P, Fimiani C, Welters I, Fricchione GL, Breton C, Lassalle P, Salzet M & Bilfinger TV 2000 Cell-surface estrogen receptors mediate calcium-dependent nitric oxide release in human endothelia. Circulation 101 1594-1597.
77. Valverde MA, Rojas P, Amigo J, Cosmelli D, Orio P, Bahamonde MI, Mann GE, Vergara C & Latorre R 1999 Acute activation of Maxi-K channels (hSlo) by estradiol binding to the beta subunit. Science 285 1929-1931.
78. Watson CS, Campbell CH & Gametchu B 1999a Membrane oestrogen receptors on rat pituitary tumour cells: immuno-identification and responses to oestradiol and xenoestrogens. Experimental Physiology 84 1013-1022.
79. Watson CS, Norfleet AM, Pappas TC & Gametchu B 1999b Rapid actions of estrogens in GH3/B6 pituitary tumor cells via a plasma membrane version of estrogen receptor-alpha. Steroids 64 5-13.
80. Welshons WV & Jordan VC 1987 Adaptation of estrogen-dependent MCF-7 cells to low estrogen (phenol red-free) culture. European Journal of Cancer and Clinical Oncology 23 1935-1939.
81. Yager JD 2000 Endogenous estrogens as carcinogens through metabolic activation. Journal of the National Cancer Institute. Monographs 27 67-73.
82. Yager JD & Liehr JG 1996 Molecular mechanisms of estrogen carcinogenesis. Annual Review of Pharmacology and Toxicology 36 203-232.
83. Yue W 2003 Genotoxic metabolites of estradiol in breast: potential mechanism of estradiol induced carcinogenesis. Journal of Steroid Biochemistry and Molecular Biology (In Press).
84. Yue W & Santen RJ 1996 Aromatase inhibitors: rationale for use following antiestrogen therapy. Seminars in Oncology 23 21-27.
85. Yue W, Wang JP, Hamilton CJ, Demers LM & Santen RJ 1998 In situ aromatization enhances breast tumor estradiol levels and cellular proliferation. Cancer Research 58 927-932.
86. Yue W, Wang JP, Conaway M, Masumura S, Li Y & Santen RJ 2002 Activation the MAPK pathway enhances sensitivity of MCF-7 breast cancer cells to the mitogenic effect of estradiol. Endocrinology 143 3221-3229.
87. Yue W, Wang J-P & Santen RJ 2003 Dual role of MAP kinase and PI-3-kinase pathways in mediation of adaptive hypersensitivity to estradiol. Journal of Steroid Biochemistry and Molecular Biology (In Press).
88. Zhang Z, Maier B, Santen RJ & Song RX 2002 Membrane association of estrogen receptor alpha mediates estrogen effect on MAPK activation. Biochemical and Biophysical Research Communications 294 926-933.