ErbB receptors and their ligands in the breast

Expert Reviews in Molecular Medicine

Volumn 8, Issue 23, 2006, Pages 1-21

  Zahnow, Cynthia A ^a  

^a JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 [4 (4 ETHYL 1 PIPERAZINYLMETHYL)PHENYL] 4 (ALPHA METHYLBENZYLAMINO) 7H PYRROLO[2,3 D]PYRIMIDINE; ANASTROZOLE; ANTINEOPLASTIC AGENT; AP 23573; AROMATASE INHIBITOR; BIBW 2992; CANERTINIB; CETUXIMAB; CP 751871; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 3; EPIDERMAL GROWTH FACTOR RECEPTOR 4; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; EVEROLIMUS; FULVESTRANT; GEFITINIB; HKI 272; LAPATINIB; LETROZOLE; LIGAND; MATUZUMAB; PANITUMUMAB; PERIFOSINE; PERTUZUMAB; TAMOXIFEN; TEMSIROLIMUS; TRASTUZUMAB; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AUTOPHOSPHORYLATION; BREAST CANCER; BREAST CARCINOGENESIS; BREAST DEVELOPMENT; CANCER GROWTH; CLINICAL TRIAL; DRUG MECHANISM; DRUG TARGETING; EMBRYO DEVELOPMENT; ENZYME ACTIVITY; GENE FUNCTION; GENE OVEREXPRESSION; GENETIC CODE; HUMAN; METASTASIS POTENTIAL; NONHUMAN; ONCOGENE; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN DETERMINATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; PROTEIN VARIANT; REVIEW; SIGNAL TRANSDUCTION; TRANSACTIVATION;

ANIMALS; BREAST; BREAST NEOPLASMS; FEMALE; HUMANS; LIGANDS; RECEPTORS, GROWTH FACTOR; SIGNAL TRANSDUCTION; TRANS-ACTIVATION (GENETICS);

EID: 33749074278     PISSN: 14623994     EISSN: 14623994     Source Type: Journal    
DOI: 10.1017/S146239940600010X     Document Type: Review

References (160)

1. Schlessinger, J. (2000) Cell signaling by receptor tyrosine kinases. Cell 103, 211-225
2. Carpenter, G. et al. (1975) Characterization of the binding of 125-I-labeled epidermal growth factor to human fibroblasts. J Biol Chem 250, 4297-4304
3. Carpenter, G., King, L., Jr and Cohen, S. (1978) Epidermal growth factor stimulates phosphorylation in membrane preparations in vitro. Nature 276, 409-410
4. Padhy, L.C. et al. (1982) Identification of a phosphoprotein specifically induced by the transforming DNA of rat neuroblastomas. Cell 28, 865-871
5. Schechter, A.L. et al. (1984) The neu oncogene: An erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature 312, 513-516
6. Kraus, M.H. et al. (1989) Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors. Proc Natl Acad Sci U S A 86, 9193-9197
7. Plowman, G.D. et al. (1990) Molecular cloning and expression of an additional epidermal growth factor receptor-related gene. Proc Natl Acad Sci U S A 87, 4905-4909
8. Plowman, G.D. et al. (1993) Ligand-specific activation of HER4/ p180erbB4, a fourth member of the epidermal growth factor receptor family. Proc Natl Acad Sci U S A 90, 1746-1750
9. Downward, J. et al. (1984) Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 307, 521-527
10. Burgess, A.W. et al. (2003) An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. Mol Cell 12, 541-552
11. Carpenter, G. (2003) ErbB-4: Mechanism of action and biology. Exp Cell Res 284, 66-77
12. Stein, R.A. and Staros, J.V. (2000) Evolutionary analysis of the ErbB receptor and ligand families. J Mol Evol 50, 397-412
13. Yarden, Y. and Sliwkowski, M.X. (2001) Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2, 127-137
14. Harris, R.C., Chung, E. and Coffey, R.J. (2003) EGF receptor ligands. Exp Cell Res 284, 2-13
15. Olayioye, M.A. et al. (2000) The ErbB signaling network: Receptor heterodimerization in development and cancer. EMBO J 19, 3159-3167
16. Hynes, N.E. and Lane, H.A. (2005) ERBB receptors and cancer: The complexity of targeted inhibitors. Nat Rev Cancer 5, 341-354
17. Cohen, S. (1962) Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem 237, 1555-1562
18. Todaro, G.J., Fryling, C. and De Larco, J.E. (1980) Transfonning growth factors produced by certain human tumor cells: Polypeptides that interact with epidermal growth factor receptors. Proc Natl Acad Sci U S A 77, 5258-5262
19. Shoyab, M. et al. (1988) Amphiregulin: A bifunctional growth-modulating glycoprotein produced by the phorbol 12-myristate 13-acetate-treated human breast adenocarcinoma cell line MCF-7. Proc Natl Acad Sci U S A 85, 6528-6532
20. Strachan, L. et al. (2001) Cloning and biological activity of epigen, a novel member of the epidermal growth factor superfamily. J Biol Chem 276, 18265-18271
21. Higashiyama, S. et al. (1992) Structure of heparin-binding EGF-like growth factor. Multiple forms, primary structure, and glycosylation of the mature protein. J Biol Chem 267, 6205-6212
22. Shing, Y. et al. (1993) Betacellulin: A mitogen from pancreatic beta cell tumors. Science 259, 1604-1607
23. Sasada, R. et al. (1993) Cloning and expression of cDNA encoding human betacellulin, a new member of the EGF family. Biochem Biophys Res Commun 190, 1173-1179
24. Toyoda, H. et al. (1995) Epiregulin. A novel epidermal growth factor with mitogenic activity for rat primary hepatocytes. J Biol Chem 270, 7495-7500
25. Falls, D.L. (2003) Neuregulins: Functions, forms, and signaling strategies. Exp Cell Res 284, 14-30
26. Uchida, T. et al. (1999) A novel epidermal growth factor-like molecule containing two follistatin modules stimulates tyrosine phosphorylation of erbB-4 in MKN28 gastric cancer cells. Biochem Biophys Res Commun 266, 593-602
27. Peles, E. and Yarden, Y. (1993) Neu and its ligands: From an oncogene to neural factors. Bioessays 15, 815-824
28. Massague, J. and Pandiella, A. (1993) Membrane-anchored growth factors. Annu Rev Biochem 62, 515-541
29. Singh, A.B. and Harris, R.C. (2005) Autocrine, paracrine and juxtacrine signaling by EGFR ligands. Cell Signal 17, 1183-1193
30. Schlessinger, J. (2002) Ligand-induced, receptor-mediated dimerization and activation of EGF receptor. Cell 110, 669-672
31. Ferguson, K.M. et al. (2003) EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization. Mol Cell 11, 507-517
32. Bouyain, S. et al. (2005) The extracellular region of ErbB4 adopts a tethered conformation in the absence of ligand. Proc Natl Acad Sci U S A 102, 15024-15029
33. Citri, A., Skaria, K.B. and Yarden, Y. (2003) The deaf and the dumb: The biology of ErbB-2 and ErbB-3. Exp Cell Res 284, 54-65
34. Leahy, D.J. (2004) Structure and function of the epidermal growth factor (EGF/ErbB) family of receptors. Adv Protein Chem 68, 1-27
35. Jorissen, R.N. et al. (2003) Epidermal growth factor receptor: mechanisms of activation and signalling. Exp Cell Res 284, 31-53
36. Schlessinger, J. (1988) Signal transduction by allosteric receptor oligomerization. Trends Biochem Sci 13, 443-447
37. Klapper, L.N. et al. (1999) The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors. Proc Natl Acad Sci U S A 96, 4995-5000
38. Ramsauer, V.P. et al. (2003) Muc4/sialomucin complex, the intramembrane ErbB2 ligand, translocates ErbB2 to the apical surface in polarized epithelial cells. J Biol Chem 278, 30142-30147
39. Garrett, T.P. et al. (2003) The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors. Mol Cell 11, 495-505
40. Cho, H.S. et al. (2003) Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 421, 756-760
41. Karunagaran, D. et al. (1996) ErbB-2 is a common auxiliary subunit of NDF and EGF receptors: Implications for breast cancer. EMBO J 15, 254-264
42. Graus-Porta, D. et al. (1997) ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J 16, 1647-1655
43. Holbro, T., Civenni, G. and Hynes, N.E. (2003) The ErbB receptors and their role in cancer progression. Exp Cell Res 284, 99-110
44. Guy, P.M. et al. (1994) Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase activity. Proc Natl Acad Sci U S A 91, 8132-8136
45. Kim, H.H. et al. (1998) Signal transduction by epidermal growth factor and heregulin via the kinase-deficient ErbB3 protein. Biochem J 334(Pt 1), 189-195
46. Songyang, Z. et al. (1993) SH2 domains recognize specific phosphopeptide sequences. Cell 72, 767-778
47. Prigent, S.A. and Gullick, W.J. (1994) Identification of c-erbB-3 binding sites for phosphatidylinositol 3′-kinase and SHC using an EGF receptor/c-erbB-3 chimera. EMBO J 13, 2831-2841
48. Zhang, X. et al. (2006) An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Cell 125, 1137-1149
49. Peschon, J.J. et al. (1998) An essential role for ectodomain shedding in mammalian development. Science 282, 1281-1284
50. Sunnarborg, S.W. et al. (2002) Tumor necrosis factor-alpha converting enzyme (TACE) regulates epidermal growth factor receptor ligand availability. J Biol Chem 277, 12838-12845
51. King, C.R. et al. (1989) Ligand-independent tyrosine phosphorylation of EGF receptor and the erbB-2/neu proto-oncogene product is induced by hyperosmotic shock. Oncogene 4, 13-18
52. Daub, H. et al. (1996) Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors. Nature 379, 557-560
53. Gutkind, J.S. (1998) Cell growth control by G protein-coupled receptors: from signal transduction to signal integration. Oncogene 17, 1331-1342
54. Zwick, E. et al. (1999) The EGF receptor as central transducer of heterologous signalling systems. Trends Pharmacol Sci 20, 408-412
55. Prenzel, N. et al. (1999) EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHBEGF Nature 402, 884-888
56. Daub, H. et al. (1997) Signal characteristics of G protein-transactivated EGF receptor. EMBO J 16, 7032-7044
57. Eguchi, S. et al. (1998) Calcium-dependent epidermal growth factor receptor transactivation mediates the angiotensin II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells. J Biol Chem 273, 8890-8896
58. Tsai, W., Morielli, A.D. and Peralta, E.G. (1997) The m1 muscarinic acetylcholine receptor transactivates the EGF receptor to modulate ion channel activity. EMBO J 16, 4597-4605
59. Keates, S. et al. (2001) cag + Helicobacter pylori induce transactivation of the epidermal growth factor receptor in AGS gastric epithelial cells. J Biol Chem 276, 48127-48134
60. Fischer, O.M. et al. (2003) EGFR signal transactivation in cancer cells. Biochem Soc Trans 31, 1203-1208
61. Roudabush, F.L. et al. (2000) Transactivation of the EGF receptor mediates IGF-1-stimulated shc phosphorylation and ERK1/2 activation in COS-7 cells. J Biol Chem 275, 22583-22589
62. Gilmore, A.P et al. (2002) Activation of BAD by therapeutic inhibition of epidermal growth factor receptor and transactivation by insulin-like growth factor receptor. J Biol Chem 277, 27643-27650
63. Civenni, G., Holbro, T. and Hynes, N.E. (2003) Wnt1 and Wnt5a induce cyclin D1 expression through ErbB1 transactivation in HC11 mammary epithelial cells. EMBO Rep 4, 166-171
64. Razandi, M. et al. (2003) Proximal events in signaling by plasma membrane estrogen receptors. J Biol Chem 278, 2701-2712
65. Daniel, C.W. and Silberstein, G.B. (1987) Postnatal development of the rodent mammary gland. In The Mammary Gland (Neville, M.C. and Daniel, C.W., eds), pp. 3-31, Plenum Press
66. Medina, D. (1996) The mammary gland: A unique organ for the study of development and tumorigenesis. J Mammary Gland Biol Neoplasia 1, 5-19
67. Schroeder, J.A. and Lee, D.C. (1998) Dynamic expression and activation of ERBB receptors in the developing mouse mammary gland. Cell Growth Differ 9, 451-464
68. Luetteke, N.C. et al. (1999) Targeted inactivation of the EGF and amphiregulin genes reveals distinct roles for EGF receptor ligands in mouse mammary gland development. Development 126, 2739-2750
69. Matsui, Y. et al. (1990) Development of mammary hyperplasia and neoplasia in MMTV-TGF alpha transgenic mice. Cell 61, 1147-1155
70. Sandgren, E.P. et al. (1990) Overexpression of TGF alpha in transgenic mice: Induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Cell 61, 1121-1135
71. Sandgren, E.P. et al. (1995) Inhibition of mammary gland involution is associated with transforming growth factor alpha but not c-myc-induced tumorigenesis in transgenic mice. Cancer Res 55, 3915-3927
72. Yang, Y. et al. (1995) Sequential requirement of hepatocyte growth factor and neuregulin in the morphogenesis and differentiation of the mammary gland. J Cell Biol 131, 215-226
73. Sternlicht, M.D. et al. (2005) Mammary ductal morphogenesis requires paracrine activation of stromal EGFR via ADAM17-dependent shedding of epithelial amphiregulin. Development 132, 3923-3933
74. Jones, F.E. et al. (1996) Heregulin induces in vivo proliferation and differentiation of mammary epithelium into secretory lobuloalveoli. Cell Growth Differ 7, 1031-1038
75. Krane, I.M. and Leder, P. (1996) NDF/heregulin induces persistence of terminal end buds and adenocarcinomas in the mammary glands of transgenic mice. Oncogene 12, 1781-1788
76. Sebastian, J. et al. (1998) Activation and function of the epidermal growth factor receptor and erbB-2 during mammary gland morphogenesis. Cell Growth Differ 9, 777-785
77. Wiesen, J.F. et al. (1999) Signaling through the stromal epidermal growth factor receptor is necessary for mammary ductal development. Development 126, 335-344
78. Jones, F.E. et al. (1999) ErbB4 signaling in the mammary gland is required for lobuloalveolar development and Stat5 activation during lactation. J Cell Biol 147, 77-88
79. Long, W. et al. (2003) Impaired differentiation and lactational failure of Erbb4-deficient mammary glands identify ERBB4 as an obligate mediator of STAT5. Development 130, 5257-5268
80. Tidcombe, H. et al. (2003) Neural and mammary gland defects in ErbB4 knockout mice genetically rescued from embryonic lethality. Proc Natl Acad Sci U S A 100, 8281-8286
81. Xie, W. et al. (1997) Targeted expression of a dominant negative epidermal growth factor receptor in the mammary gland of transgenic mice inhibits pubertal mammary duct development. Mol Endocrinol. 11, 1766-1781
82. Fowler, K.J. et al. (1995) A mutation in the epidermal growth factor receptor in waved-2 mice has a profound effect on receptor biochemistry that results in impaired lactation. Proc Natl Acad Sci U S A 92, 1465-1469
83. Jones, F.E. and Stern, D.F. (1999) Expression of dominant-negative ErbB2 in the mammary gland of transgenic mice reveals a role in lobuloalveolar development and lactation. Oncogene 18, 3481-3490
84. Bouchard, L. et al. (1989) Stochastic appearance of mammary tumors in transgenic mice carrying the MMTV/c-neu oncogene. Cell 57, 931-936
85. Lucchini, F. et al. (1992) Early and multifocal tumors in breast, salivary, harderian and epididymal tissues developed in MMTY-Neu transgenic mice. Cancer Lett 64, 203-209
86. Guy, C.T., Cardiff, R.D. and Muller, W.J. (1996) Activated neu induces rapid tumor progression. J Biol Chem 271, 7673-7678
87. Guy, C.T., Cardiff, R.D. and Muller, W.J. (1992) Induction of mammary tumors by expression of polyomavirus middle T oncogene: A transgenic mouse model for metastatic disease. Mol Cell Biol 12, 954-961
88. Siegel, P.M. et al. (1994) Novel activating mutations in the neu proto-oncogene involved in induction of mammary tumors. Mol Cell Biol 14, 7068-7077
89. Jackson-Fisher, A.J. et al. (2006) Formation of Neu/ErbB2-induced mammary umors is unaffected by loss of ErbB4. Oncogene doi: 10.1038/ sj.onc.1209574
90. Bhargava, R. et al. (2005) EGFR gene amplification in breast cancer: correlation with epidermal growth factor receptor mRNA and protein expression and HER-2 status and absence of EGFR-activating mutations. Mod Pathol 18, 1027-1033
91. Al, Kuraya, K. et al. (2004) Prognostic relevance of gene amplifications and coamplifications in breast cancer. Cancer Res 64, 8534-8540
92. Lewis, S. et al. (1990) Expression of epidermal growth factor receptor in breast carcinoma. J Clin Pathol 43, 385-389
93. Toi, M. et al. (1990) Relationship between epidermal growth factor receptor status and various prognostic factors in human breast cancer. Cancer 65, 1980-1984
94. Walker, R.A. and Dearing, S.J. (1999) Expression of epidermal growth factor receptor mRNA and protein in primary breast carcinomas. Breast Cancer Res Treat 53, 167-176
95. Kersting, C. et al. (2006) Amplifications of the epidermal growth factor receptor gene (egfr) are common in phyllodes tumors of the breast and are associated with tumor progression. Lab Invest 86, 54-61
96. Reis-Filho, J.S. et al. (2005) Metaplastic breast carcinomas exhibit EGFR, but not HER2, gene amplification and overexpression: immunohistochemical and chromogenic in situ hybridization analysis. Breast Cancer Res 7, R1028-R1035
97. Shien, T. et al. (2005) Frequent overexpression of epidermal growth factor receptor (EGFR) in mammary high grade ductal carcinomas with myoepithehal differentiation. J Clin Pathol 58, 1299-1304
98. Slamon, D.J. et al. (1987) Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235, 177-182
99. Ross, J.S. and Fletcher, J.A. (1998) The HER-2/neu oncogene in breast cancer: Prognostic factor, predictive factor, and target for therapy. Oncologist 3, 237-252
100. Allred, D.C. et al. (1992) Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. Hum Pathol 23, 974-979
101. Bates, N.P. and Hurst, H.C. (1997) Transcriptional regulation of type I receptor tyrosine kinases in the mammary gland. J Mammary Gland Biol Neoplasia 2, 153-163
102. Di Fiore, P.P. et al. (1987) erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. Science 237, 178-182
103. Hudziak, R.M., Schlessinger, J. and Ullrich, A. (1987) Increased expression of the putative growth factor receptor p185HER2 causes transformation and tumorigenesis of NIH 3T3 cells. Proc Natl Acad Sci U S A 84, 7159-7163
104. Witton, C.J. et al. (2003) Expression of the HER1-4 family of receptor tyrosine kinases in breast cancer. J Pathol 200, 290-297
105. Naidu, R. et al. (1998) Expression of c-erbB3 protein in primary breast carcinomas. Br J Cancer 78, 1385-1390
106. Gasparini, G. et al. (1994) c-erbB-3 and c-erbB-2 protein expression in node-negative breast carcinoma - an immunocytochemical study. Eur J Cancer 30A, 16-22
107. Gullick, W.J. (2003) c-erbB4/HER4: Friend or foe? J Pathol 200, 279-281
108. Elenius, K. et al. (1997) A novel juxtamembrane domain isoform of HER4/ ErbB4. Isoform-specific tissue distribution and differential processing in response to phorbol ester. J Biol Chem 272, 26761-26768
109. Junttila, T.T. et al. (2003) Identification of patients with transitional cell carcinoma of the bladder overexpressing ErbB2, ErbB3, or specific ErbB4 isoforms: Real-time reverse transcription-PCR analysis in estimation of ErbB receptor status from cancer patients. Clin Cancer Res 9, 5346-5357
110. Srinivasan, R. et al. (1998) Expression of the c-erbB4/HER4 protein and mRNA in normal human fetal and adult tissues and in a survey of nine solid tumour types. J Pathol 185, 236-245
111. Ni, C.Y. et al. (2001) gamma -Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science 294, 2179-2181
112. Srinivasan, R. et al. (2000) Nuclear expression of the c-erbB-4/HER-4 growth factor receptor in invasive breast cancers. Cancer Res 60, 1483-1487
113. Junttila, T.T. et al. (2005) Cleavable ErbB4 isoform in estrogen receptor-regulated growth of breast cancer cells. Cancer Res 65, 1384-1393
114. Muraoka-Cook, R.S. et al. (2006) The intracellular domain of ErbB4 induces differentiation of mammary epithelial cells. Mol Biol Cell 17, 4118-4129
115. Naresh, A. et al. (2006) The ERBB4/HER4 intracellular domain 4ICD is a BH3-only protein promoting apoptosis of breast cancer cells. Cancer Res 66, 6412-6420
116. Suo, Z. et al. (2001) Estrogen receptor-alpha and C-ERBB-4 expression in breast carcinomas. Virchows Arch 439, 62-69
117. Sartor, C.I. et al. (2001) Her4 mediates ligand-dependent antiproliferative and differentiation responses in human breast cancer cells. Mol Cell Biol 21, 4265-4275
118. Bieche, I. et al. (2003) Prognostic value of ERBB family mRNA expression in breast carcinomas. Int J Cancer 106, 758-765
119. Lodge, A.J. et al. (2003) Type 1 growth factor receptor expression in node positive breast cancer: Adverse prognostic significance of c-erbB-4. J Clin Pathol 56, 300-304
120. Vogt, U. et al. (1998) Amplification of erbB-4 oncogene occurs less frequently than that of erbB-2 in primary human breast cancer. Gene 223, 375-380
121. Petch, L.A. et al. (1990) A truncated, secreted form of the epidermal growth factor receptor is encoded by an alternatively spliced transcript in normal rat tissue. Mol Cell Biol 10, 2973-2982
122. Lee, H. et al. (2001) A naturally occurring secreted human ErbB3 receptor isoform inhibits heregulin-stimulated activation of ErbB2, ErbB3, and ErbB4. Cancer Res 61, 4467-4473
123. Kwong, K.Y. and Hung, M.C. (1998) A novel splice variant of HER2 with increased transformation activity. Mol Carcinog 23, 62-68
124. Christianson, T.A. et al. (1998) NH2-terminally truncated HER-2/neu protein: Relationship with shedding of the extracellular domain and with prognostic factors in breast cancer. Cancer Res 58, 5123-5129
125. Doherty J.K. et al. (1999) The HER-2/neu receptor tyrosine kinase gene encodes a secreted autoinhibitor. Proc Natl Acad Sci U S A 96, 10869-10874
126. Azios, N.G. et al. (2001) Expression of herstatin, an autoinhibitor of HER-2/neu, inhibits transactivation of HER-3 by HER-2 and blocks EGF activation of the EGF receptor. Oncogene 20, 5199-5209
127. Lin, S.Y. et al. (2001) Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nat Cell Biol 3, 802-808
128. Massie, C. and Mills, I.G. (2006) The developing role of receptors and adaptors. Nat Rev Cancer 6, 403-409
129. Sweeney, C. and Carraway, K.L., III (2004) Negative regulation of ErbB family receptor tyrosine kinases. Br J Cancer 90, 289-293
130. Sweeney, C. et al. (2006) ErbB receptor negative regulatory mechanisms: implications in cancer. J Mammary Gland Biol Neoplasia 11, 89-99
131. Rubin, C., Gur, G. and Yarden, Y. (2005) Negative regulation of receptor tyrosine kinases: Unexpected links to c-Cbl and receptor ubiquitylation. Cell Res 15, 66-71
132. Baulida, J. et al. (1996) All ErbB receptors other than the epidermal growth factor receptor are endocytosis impaired. J Biol Chem 271, 5251-5257
133. Levkowitz, G. et al. (1996) Coupling of the c-Cbl protooncogene product to ErbB-1/EGF-receptor but not to other ErbB proteins. Oncogene 12, 1117-1125
134. Baselga, J. and Arteaga, C.L. (2005) Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol 23, 2445-2459
135. Nahta, R. et al. (2006) Mechanisms of disease: Understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol 3, 269-280
136. Cuello, M. et al. (2001) Down-regulation of the erbB-2 receptor by trastuzumab (herceptin) enhances tumor necrosis factor-related apoptosis inducing ligand-mediated apoptosis in breast and ovarian cancer cell lines that overexpress erbB-2. Cancer Res 61, 4892-4900
137. Lane, H.A. et al. (2001) Modulation of p27/Cdk2 complex formation through 4D5-mediated inhibition of HER2 receptor signaling. Ann Oncol 12 Suppl 1, S21-S22
138. Nagata, Y. et al. (2004) PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 6, 117-127
139. Arnould, L. et al. (2006) Trastuzumab-based treatment of HER2-positive breast cancer: An antibody-dependent cellular cytotoxicity mechanism? Br J Cancer 94, 259-267
140. Stein, M.N. et al. (2006) Antibody-dependent cell cytotoxicity to breast cancer targets despite inhibitory KIR signaling. Anticancer Res 26, 1759-1763
141. Vogel, C.L. et al. (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20, 719-726
142. Stern, D.F. (2000) Tyrosine kinase signalling in breast cancer: ErbB family receptor tyrosine kinases. Breast Cancer Res 2, 176-183
143. Franklin, M.C. et al. (2004) Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell 5, 317-328
144. Agus, D.B. et al. (2005) Phase I clinical study of pertuzumab, a novel HER dimerization inhibitor, in patients with advanced cancer. J Clin Oncol 23, 2534-2543
145. Price-Schiavi, S.A. et al. (2002) Rat Muc4 (sialomucin complex) reduces binding of anti-ErbB2 antibodies to tumor cell surfaces, a potential mechanism for herceptin resistance. Int J Cancer 99, 783-791
146. Nagy, P. et al. (2005) Decreased accessibility and lack of activation of ErbB2 in JIMT-1, a herceptin-resistant, MUC4-expressing breast cancer cell line. Cancer Res 65, 473-482
147. Spector, N.L. et al. (2005) Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies. J Clin Oncol 23, 2502-2512
148. Allen, L.F. et al. (2002) Potential benefits of the irreversible pan-erbB inhibitor, CI-1033, in the treatment of breast cancer. Semin Oncol 29, 11-21
149. Chakravarti, A., Loeffler, J.S. and Dyson, N.J. (2002) Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling. Cancer Res 62, 200-207
150. Scotlandi, K. et al. (2005) Antitumor activity of the insulin-like growth factor-I receptor kinase inhibitor NVP-AEW541 in musculoskeletal tumors. Cancer Res 65, 3868-3876
151. Cohen, B.D. et al. (2005) Combination therapy enhances the inhibition of tumor growth with the fully human anti-type 1 insulin-like growth factor receptor monoclonal antibody CP-751, 871. Clin Cancer Res 11, 2063-2073
152. Lu, Y. et al. (2001) Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (Herceptin). J Natl Cancer Inst 93, 1852-1857
153. Shang, Y. (2006) Molecular mechanisms of oestrogen and SERMs in endometrial carcinogenesis. Nat Rev Cancer 6, 360-368
154. Matsuda, S. et al. (1993) 17 beta-estradiol mimics ligand activity of the c-erbB2 protooncogene product. Proc Natl Acad Sci U S A 90, 10803-10807
155. Osbome, C.K. et al. (2005) Crosstalk between estrogen receptor and growth factor receptor pathways as a cause for endocrine therapy resistance in breast cancer. Clin Cancer Res 11, 865s-870s
156. Ellis, M. (2004) Overcoming endocrine therapy resistance by signal transduction inhibition. Oncologist 9 Suppl 3, 20-26
157. Gee, J.M. et al. (2003) The antiepidermal growth factor receptor agent gefitinib (ZD1839/Iressa) improves antihormone response and prevents development of resistance in breast cancer in vitro. Endocrinology 144, 5105-5117
158. Chung, Y.L. et al. (2002) Resistance to tamoxifen-induced apoptosis is associated with direct interaction between Her2/neu and cell membrane estrogen receptor in breast cancer. Int J Cancer 97, 306-312
159. Garrett, T.P. et al. (2002) Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha. Cell 110, 763-773
160. Ogiso, H. et al. (2002) Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains. Cell 110, 775-787