Epidermal growth factor receptor (EGFR) signaling in cancer

Aaronson, 1991, Growth factors and cancer, Science, 254, 1146, 10.1126/science.1659742 Abbott, 2003, Lack of expression of EGF and TGF-alpha in the fetal mouse alters formation of prostatic epithelial buds and influences the response to TCDD, Toxicol. Sci., 76, 427, 10.1093/toxsci/kfg238 Abd El-Rehim, 2004, Expression and co-expression of the members of the epidermal growth factor receptor (EGFR) family in invasive breast carcinoma, Br. J. Cancer, 91, 1532, 10.1038/sj.bjc.6602184 Alimandi, 1995, Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas, Oncogene, 10, 1813 Andl, 2003, Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo, J. Biol. Chem., 278, 1824, 10.1074/jbc.M209148200 Anido, 2003, ZD1839, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, induces the formation of inactive EGFR/HER2 and EGFR/HER3 heterodimers and prevents heregulin signaling in HER2-overexpressing breast cancer cells, Clin. Cancer Res., 9, 1274 Bhargava, 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, 10.1038/modpathol.3800438 Ben-Levy, 1994, A single autophosphorylation site confers oncogenicity to the Neu/ErbB-2 receptor and enables coupling to the MAP kinase pathway, EMBO J., 13, 3302, 10.1002/j.1460-2075.1994.tb06632.x Biscardi, 1999, c-Src-mediated phosphorylation of the epidermal growth factor receptor on Tyr845 and Tyr1101 is associated with modulation of receptor function, J. Biol. Chem., 274, 8335, 10.1074/jbc.274.12.8335 Biswas, 2000, Epidermal growth factor-induced nuclear factor kappa B activation: a major pathway of cell-cycle progression in estrogen-receptor negative breast cancer cells, Proc. Natl. Acad. Sci. U. S. A., 97, 8542, 10.1073/pnas.97.15.8542 Blum, 1998, A null mutation in TGF-alpha leads to a reduction in midbrain dopaminergic neurons in the substantia nigra, Nat. Neurosci., 1, 374, 10.1038/1584 Bol, 1998, Severe follicular hyperplasia and spontaneous papilloma formation in transgenic mice expressing the neu oncogene under the control of the bovine keratin 5 promoter, Mol. Carcinog., 21, 2, 10.1002/(SICI)1098-2744(199801)21:1<2::AID-MC2>3.0.CO;2-R Brabender, 2001, Epidermal growth factor receptor and HER2-neu mRNA expression in non-small cell lung cancer is correlated with survival, Clin. Cancer Res., 7, 1850 Brandt, 2000, Mammary gland specific hEGF receptor transgene expression induces neoplasia and inhibits differentiation, Oncogene, 19, 2129, 10.1038/sj.onc.1203520 Campbell, 1993, Epidermal growth factor-like modules, Curr. Opin. Struct. Biol., 3, 385, 10.1016/S0959-440X(05)80111-3 Campiglio, 2004, Inhibition of proliferation and induction of apoptosis in breast cancer cells by the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (‘Iressa') is independent of EGFR expression level, J. Cell. Physiol., 198, 259, 10.1002/jcp.10411 Cappuzzo, 2005, Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer, J. Natl. Cancer Inst., 97, 643, 10.1093/jnci/dji112 Carpenter, 2000, EGF receptor transactivation mediated by the proteolytic production of EGF-like agonists, Sci. STKE 2000, E1 Carpenter, 2003, ErbB-4: mechanism of action and biology, Exp. Cell. Res., 284, 66, 10.1016/S0014-4827(02)00100-3 Carraway, 1997, Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases, Nature, 387, 512, 10.1038/387512a0 Chang, 1997, Ligands for ErbB-family receptors encoded by a neuregulin-like gene, Nature, 387, 509, 10.1038/387509a0 Chattopadhyay, 1999, The role of individual SH2 domains in mediating association of phospholipase C-gamma1 with the activated EGF receptor, J. Biol. Chem., 274, 26091, 10.1074/jbc.274.37.26091 Cheng, 2002, Overexpression of epidermal growth factor receptor in urothelium elicits urothelial hyperplasia and promotes bladder tumor growth, Cancer Res., 62, 4157 Cho, 2002, Structure of the extracellular region of HER3 reveals an interdomain tether, Science, 297, 1330, 10.1126/science.1074611 Cho, 2003, Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab, Nature, 421, 756, 10.1038/nature01392 Chou, 2005, Mutation in the tyrosine kinase domain of epidermal growth factor receptor is a predictive and prognostic factor for gefitinib treatment in patients with non-small cell lung cancer, Clin. Cancer Res., 11, 3750, 10.1158/1078-0432.CCR-04-1981 Chow, 2001, Expression profiles of ErbB family receptors and prognosis in primary transitional cell carcinoma of the urinary bladder, Clin. Cancer Res., 7, 1957 Christianson, 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 Ciardiello, 1990, Cell. Growth Differ., 1, 407 Citri, 2003, The deaf and the dumb: the biology of ErbB-2 and ErbB-3, Exp. Cell. Res., 284, 54, 10.1016/S0014-4827(02)00101-5 Civenni, 2003, Wnt1 and Wnt5a induce cyclin D1 expression through ErbB1 transactivation in HC11 mammary epithelial cells, EMBO Rep., 4, 166, 10.1038/sj.embor.embor735 Cohen, 1996, HER4-mediated biological and biochemical properties in NIH 3T3 cells, Evidence for HER1-HER4 heterodimers, J. Biol. Chem., 271, 4813, 10.1074/jbc.271.9.4813 Colomer, 2000, Circulating HER2 extracellular domain and resistance to chemotherapy in advanced breast cancer, Clin. Cancer Res., 6, 2356 Cook, 1997, Transgenic expression of the human amphiregulin gene induces a psoriasis-like phenotype, J. Clin. Invest., 100, 2286, 10.1172/JCI119766 Crone, 2002, ErbB2 is essential in the prevention of dilated cardiomyopathy, Nat. Med., 8, 459, 10.1038/nm0502-459 Cutry, 1989, Induction of c-fos and c-myc proto-oncogene expression by epidermal growth factor and transforming growth factor alpha is calcium-independent, J. Biol. Chem., 264, 19700, 10.1016/S0021-9258(19)47169-X de Larco, 1978, Growth factors from murine sarcoma virus-transformed cells, Proc. Natl. Acad. Sci. U. S. A., 75, 4001, 10.1073/pnas.75.8.4001 Di Fiore, 1987, ErbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells, Science, 237, 178, 10.1126/science.2885917 Di Fiore, 1987, Overexpression of the human EGF receptor confers an EGF-dependent transformed phenotype to NIH 3T3 cells, Cell, 51, 1063, 10.1016/0092-8674(87)90592-7 DiGiovanna, 1998, Active signaling by Neu in transgenic mice, Oncogene, 17, 1877, 10.1038/sj.onc.1202091 DiGiovanna, 2005, Relationship of epidermal growth factor receptor expression to ErbB-2 signaling activity and prognosis in breast cancer patients, J. Clin. Oncol., 23, 1152, 10.1200/JCO.2005.09.055 Di Marco, 1989, Autocrine interaction between TGF alpha and the EGF-receptor: quantitative requirements for induction of the malignant phenotype, Oncogene, 4, 831 Ding, 2003, Oligodendrogliomas result from the expression of an activated mutant epidermal growth factor receptor in a RAS transgenic mouse astrocytoma model, Cancer Res., 63, 1106 Dominey, 1993, Targeted overexpression of transforming growth factor alpha in the epidermis of transgenic mice elicits hyperplasia, hyperkeratosis, and spontaneous, squamous papillomas, Cell. Growth Differ., 4, 1071 Elenius, 1999, Characterization of a naturally occurring ErbB4 isoform that does not bind or activate phosphatidyl inositol 3-kinase, Oncogene, 18, 2607, 10.1038/sj.onc.1202612 Engelman, 2005, ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines, Proc. Natl. Acad. Sci. U. S. A., 102, 3788, 10.1073/pnas.0409773102 Erickson, 1997, ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2-and heregulin-deficient mice, Development, 124, 4999, 10.1242/dev.124.24.4999 Fazioli, 1993, eps15, a novel tyrosine kinase substrate, exhibits transforming activity, Mol. Cell. Biol., 13, 5814, 10.1128/MCB.13.9.5814 Fedi, 1994, Efficient coupling with phosphatidylinositol 3-kinase, but not phospholipase C gamma or GTPase-activating protein, distinguishes ErbB-3 signaling from that of other ErbB/EGFR family members, Mol. Cell. Biol., 14, 492, 10.1128/MCB.14.1.492 Ferguson, 2003, EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization, Mol. Cell, 11, 507, 10.1016/S1097-2765(03)00047-9 Frederick, 2000, Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas, Cancer Res., 60, 1383 French, 1995, Intracellular trafficking of epidermal growth factor family ligands is directly influenced by the pH sensitivity of the receptor/ligand interaction, J. Biol. Chem., 270, 4334, 10.1074/jbc.270.9.4334 Garrett, 2002, Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha, Cell, 110, 763, 10.1016/S0092-8674(02)00940-6 Garrett, 2003, The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors, Mol. Cell, 11, 495, 10.1016/S1097-2765(03)00048-0 Gassmann, 1995, Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor, Nature, 378, 390, 10.1038/378390a0 Golub, 2004, Behavioral characteristics of a nervous system-specific erbB4 knock-out mouse, Behav. Brain Res., 153, 159, 10.1016/j.bbr.2003.11.010 Goustin, 1986, Growth factors and cancer, Cancer Res., 46, 1015 Graus-Porta, 1997, ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling, EMBO J., 16, 1647, 10.1093/emboj/16.7.1647 Gschwind, 2001, Cell communication networks: epidermal growth factor receptor transactivation as the paradigm for interreceptor signal transmission, Oncogene, 20, 1594, 10.1038/sj.onc.1204192 Gschwind, 2002, Lysophosphatidic acid-induced squamous cell carcinoma cell proliferation and motility involves epidermal growth factor receptor signal transactivation, Cancer Res., 62, 6329 Gullick, 1990, The role of the epidermal growth factor receptor and the c-erbB-2 protein in breast cancer, Int. J. Cancer, Suppl., 5, 55, 10.1002/ijc.2910460708 Gullick, 2001, The Type 1 growth factor receptors and their ligands considered as a complex system, Endocr. Relat. Cancer, 8, 75, 10.1677/erc.0.0080075 Guy, 1992, Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease, Proc. Natl. Acad. Sci. U. S. A., 89, 10578, 10.1073/pnas.89.22.10578 Guy, 1994, Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase activity, Proc. Natl. Acad. Sci. U. S. A., 91, 8132, 10.1073/pnas.91.17.8132 Guy, 1996, Activated neu induces rapid tumor progression, J. Biol. Chem., 271, 7673, 10.1074/jbc.271.13.7673 Halter, 1992, Distinctive patterns of hyperplasia in transgenic mice with mouse mammary tumor virus transforming growth factor-alpha. Characterization of mammary gland and skin proliferations, Am. J. Pathol., 140, 1131 Han, 2005, Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small-cell lung cancer patients treated with gefitinib, J. Clin. Oncol., 23, 2493, 10.1200/JCO.2005.01.388 Harari, 1999, Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase, Oncogene, 18, 2681, 10.1038/sj.onc.1202631 Hirata, 2005, HER2 overexpression increases sensitivity to gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, through inhibition of HER2/HER3 heterodimer formation in lung cancer cells, Cancer Res., 65, 4253, 10.1158/0008-5472.CAN-04-2748 Hirsch, 2003, Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis, J. Clin. Oncol., 21, 3798, 10.1200/JCO.2003.11.069 Huang, 2004, High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan, Clin. Cancer Res., 10, 8195, 10.1158/1078-0432.CCR-04-1245 Jhappan, 1990, TGF alpha overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas, Cell, 61, 1137, 10.1016/0092-8674(90)90076-Q Jones, 1999, Expression of dominant-negative ErbB2 in the mammary gland of transgenic mice reveals a role in lobuloalveolar development and lactation, Oncogene, 18, 3481, 10.1038/sj.onc.1202698 Jones, 1999, ErbB4 signaling in the mammary gland is required for lobuloalveolar development and Stat5 activation during lactation, J. Cell. Biol., 147, 77, 10.1083/jcb.147.1.77 Jorissen, 2003, Epidermal growth factor receptor: mechanisms of activation and signalling, Exp. Cell. Res., 284, 31, 10.1016/S0014-4827(02)00098-8 Kiguchi, 2000, Constitutive expression of erbB2 in epidermis of transgenic mice results in epidermal hyperproliferation and spontaneous skin tumor development, Oncogene, 19, 4243, 10.1038/sj.onc.1203778 Klijn, 1992, The clinical significance of epidermal growth factor receptor (EGF-R) in human breast cancer: a review on 5232 patients, Endocr. Rev., 13, 3 Kobayashi, 2005, EGFR mutation and resistance of non-small-cell lung cancer to gefitinib, N. Engl. J. Med., 352, 786, 10.1056/NEJMoa044238 Kokai, 1989, Synergistic interaction of p185c-neu and the EGF receptor leads to transformation of rodent fibroblasts, Cell, 58, 287, 10.1016/0092-8674(89)90843-X Krane, 1996, NDF/heregulin induces persistence of terminal end buds and adenocarcinomas in the mammary glands of transgenic mice, Oncogene, 12, 1781 Kuan, 2001, EGF mutant receptor vIII as a molecular target in cancer therapy, Endocr. Relat. Cancer, 8, 83, 10.1677/erc.0.0080083 Lee, 1995, Requirement for neuregulin receptor erbB2 in neural and cardiac development, Nature, 378, 394, 10.1038/378394a0 Lee, 2002, Investigation of the prognostic value of coexpressed erbB family members for the survival of colorectal cancer patients after curative surgery, Eur. J. Cancer, 38, 1065, 10.1016/S0959-8049(02)00004-7 Lee, 2005, Somatic mutations of EGFR gene in squamous cell carcinoma of the head and neck, Clin. Cancer Res., 11, 2879, 10.1158/1078-0432.CCR-04-2029 Lenferink, 1998, Differential endocytic routing of homo-and hetero-dimeric ErbB tyrosine kinases confers signaling superiority to receptor heterodimers, EMBO J., 17, 3385, 10.1093/emboj/17.12.3385 Leu, 2003, Erbb2 regulates neuromuscular synapse formation and is essential for muscle spindle development, Development, 130, 2291, 10.1242/dev.00447 Levkowitz, 1998, c-Cbl/Sli-1 regulates endocytic sorting and ubiquitination of the epidermal growth factor receptor, Genes Dev., 12, 3663, 10.1101/gad.12.23.3663 Levkowitz, 1999, Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1, Mol. Cell, 4, 1029, 10.1016/S1097-2765(00)80231-2 Lin, 1991, A soluble protein related to the HER-2 proto-oncogene product is released from human breast carcinoma cells, Oncogene, 6, 639 Lu, 2003, Effect of epidermal growth factor receptor inhibitor on development of estrogen receptor-negative mammary tumors, J. Natl. Cancer Inst., 95, 1825, 10.1093/jnci/djg117 Luetteke, 1993, TGF alpha deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice, Cell, 73, 263, 10.1016/0092-8674(93)90228-I Luetteke, 1999, Targeted inactivation of the EGF and amphiregulin genes reveals distinct roles for EGF receptor ligands in mouse mammary gland development, Development, 126, 2739, 10.1242/dev.126.12.2739 Lynch, 2004, Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib, N. Engl. J. Med., 350, 2129, 10.1056/NEJMoa040938 Mann, 1993, Mice with a null mutation of the TGF alpha gene have abnormal skin architecture, wavy hair, and curly whiskers and often develop corneal inflammation, Cell, 73, 249, 10.1016/0092-8674(93)90227-H Marchetti, 2005, EGFR mutations in non-small-cell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment, J. Clin. Oncol., 23, 857, 10.1200/JCO.2005.08.043 Marmor, 2004, Role of protein ubiquitylation in regulating endocytosis of receptor tyrosine kinases, Oncogene, 23, 2057, 10.1038/sj.onc.1207390 Matsui, 1990, Development of mammary hyperplasia and neoplasia in MMTV-TGF alpha transgenic mice, Cell, 61, 1147, 10.1016/0092-8674(90)90077-R Miettinen, 1995, Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor, Nature, 376, 337, 10.1038/376337a0 Mitsudomi, 2005, Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence, J. Clin. Oncol., 23, 2513, 10.1200/JCO.2005.00.992 Moasser, 2001, The tyrosine kinase inhibitor ZD1839 (“Iressa”) inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells, Cancer Res., 61, 7184 Molina, 2002, NH(2)-terminal truncated HER-2 protein but not full-length receptor is associated with nodal metastasis in human breast cancer, Clin. Cancer Res., 8, 347 Moroni, 2005, Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study, Lancet Oncol., 6, 279, 10.1016/S1470-2045(05)70102-9 Moulder, 2001, Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo, Cancer Res., 61, 8887 Muller, 1988, Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene, Cell, 54, 105, 10.1016/0092-8674(88)90184-5 Muller, 1996, Synergistic interaction of the Neu proto-oncogene product and transforming growth factor alpha in the mammary epithelium of transgenic mice, Mol. Cell. Biol., 16, 5726, 10.1128/MCB.16.10.5726 Nagahara, 2005, Somatic mutations of epidermal growth factor receptor in colorectal carcinoma, Clin. Cancer Res., 11, 1368, 10.1158/1078-0432.CCR-04-1894 Naylor, 2002, Mouse strain-specific patterns of mammary epithelial ductal side branching are elicited by stromal factors, Dev. Dyn., 225, 100, 10.1002/dvdy.10133 Normanno, 2001, The role of EGF-related peptides in tumor growth, Front. Biosci., 6, d685, 10.2741/Normano Normanno, 2002, Cooperative inhibitory effect of ZD1839 (Iressa) in combination with trastuzumab (Herceptin) on human breast cancer cell growth, Ann. Oncol., 13, 65, 10.1093/annonc/mdf020 Normanno, 2003, Target-based agents against ErbB receptors and their ligands: a novel approach to cancer treatment, Endocr. Relat. Cancer, 10, 1, 10.1677/erc.0.0100001 Normanno, 2003, Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs): simple drugs with a complex mechanism of action?, J. Cell. Physiol., 194, 13, 10.1002/jcp.10194 Normanno, 2005, The ErbB receptors and their ligands in cancer: an overview, Curr. Drug Targets, 6, 243, 10.2174/1389450053765879 Normanno, 2005, Gefitinib inhibits the ability of human bone marrow stromal cells to induce osteoclast differentiation: implications for the pathogenesis and treatment of bone metastasis, Endocr. Relat. Cancer, 12, 471, 10.1677/erc.1.00956 Ogiso, 2002, Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains, Cell, 110, 775, 10.1016/S0092-8674(02)00963-7 O'Hagan, 1998, The PEA3 Ets transcription factor is a downstream target of the HER2/Neu receptor tyrosine kinase, Oncogene, 16, 301, 10.1038/sj.onc.1201547 Olayioye, 1999, ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases, J. Biol. Chem., 274, 17209, 10.1074/jbc.274.24.17209 Olayioye, 2000, The ErbB signaling network: receptor heterodimerization in development and cancer, EMBO J., 19, 3159, 10.1093/emboj/19.13.3159 Paez, 2004, EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy, Science, 304, 1497, 10.1126/science.1099314 Pao, 2004, EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib, Proc. Natl. Acad. Sci. U. S. A., 101, 13306, 10.1073/pnas.0405220101 Pao, 2005, Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain, PLoS Med., 2, e73, 10.1371/journal.pmed.0020073 Pao, 2005, KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib, PLoS Med., 2, e17, 10.1371/journal.pmed.0020017 Park, 2001, The erbB2 gene is required for the development of terminally differentiated spinal cord oligodendrocytes, J. Cell. Biol., 154, 1245, 10.1083/jcb.200104025 Pattengale, 1989, Animal models of human disease. Pathology and molecular biology of spontaneous neoplasms occurring in transgenic mice carrying and expressing activated cellular oncogenes, Am. J. Pathol., 135, 39 Pedersen, 2001, The type III epidermal growth factor receptor mutation. Biological significance and potential target for anti-cancer therapy, Ann. Oncol., 12, 745, 10.1023/A:1011177318162 Prenzel, 1999, EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF, Nature, 402, 884, 10.1038/47260 Prigent, 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, 10.1002/j.1460-2075.1994.tb06577.x Pupa, 1993, The extracellular domain of the c-erbB-2 oncoprotein is released from tumor cells by proteolytic cleavage, Oncogene, 8, 2917 Quantin, 1988, Epidermal growth factor stimulates transcription of the c-Jun proto-oncogene in rat fibroblasts, Nature, 334, 538, 10.1038/334538a0 Ravdin, 1995, The c-erbB-2 proto-oncogene as a prognostic and predictive marker in breast cancer: a paradigm for the development of other macromolecular markers—a review, Gene, 159, 19, 10.1016/0378-1119(94)00866-Q Rosenthal, 1986, Expression in rat fibroblasts of a human transforming growth factor-alpha cDNA results in transformation, Cell, 46, 301, 10.1016/0092-8674(86)90747-6 Salomon, 1990, Transforming growth factor-α: an oncodevelopmental growth factor, Cancer Cells, 2, 389 Salomon, 1995, Epidermal growth factor-related peptides and their receptors in human malignancies, Crit. Rev. Oncol. Hematol., 19, 183, 10.1016/1040-8428(94)00144-I Sandgren, 1990, Overexpression of TGF alpha in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast, Cell, 61, 1121, 10.1016/0092-8674(90)90075-P Sandgren, 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 Schlessinger, 2000, Cell signaling by receptor tyrosine kinases, Cell, 103, 211, 10.1016/S0092-8674(00)00114-8 Segatto, 1988, Different structural alterations upregulate in vitro tyrosine kinase activity and transforming potency of the erbB-2 gene, Mol. Cell. Biol., 8, 5570, 10.1128/MCB.8.12.5570 Shankar, 1989, Transformation of an established mouse mammary epithelial cell line following transfection with a human transforming growth factor alpha cDNA, Mol. Carcinog., 2, 1, 10.1002/mc.2940020102 Shigematsu, 2005, and biological features associated with epidermal growth factor receptor gene mutations in lung cancers, J. Natl. Cancer Inst., 97, 339, 10.1093/jnci/dji055 Shigematsu, 2005, Somatic mutations of the HER2 kinase domain in lung adenocarcinomas, Cancer Res., 65, 1642, 10.1158/0008-5472.CAN-04-4235 Shinojima, 2003, Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme, Cancer Res., 63, 6962 Sibilia, 1995, Strain-dependent epithelial defects in mice lacking the EGF receptor, Science, 269, 234, 10.1126/science.7618085 Sibilia, 1998, A strain-independent postnatal neurodegeneration in mice lacking the EGF receptor, EMBO J., 17, 719, 10.1093/emboj/17.3.719 Siegel, 1996, Mutations affecting conserved cysteine residues within the extracellular domain of Neu promote receptor dimerization and activation, Proc. Natl. Acad. Sci. U. S. A., 93, 8878, 10.1073/pnas.93.17.8878 Siegel, 1994, Novel activating mutations in the neu proto-oncogene involved in induction of mammary tumors, Mol. Cell. Biol., 14, 7068, 10.1128/MCB.14.11.7068 Siegel, 1999, Elevated expression of activated forms of Neu/ErbB-2 and ErbB-3 are involved in the induction of mammary tumors in transgenic mice: implications for human breast cancer, EMBO J., 18, 2149, 10.1093/emboj/18.8.2149 Singer, 2004, Expression of tyrosine kinases in human malignancies as potential targets for kinase-specific inhibitors, Endocr. Relat. Cancer, 11, 861, 10.1677/erc.1.00801 Soltoff, 1996, p120cbl is a cytosolic adapter protein that associates with phosphoinositide 3-kinase in response to epidermal growth factor in PC12 and other cells, J. Biol. Chem., 271, 563, 10.1074/jbc.271.1.563 Sorkin, 1993, Endocytosis of growth factor receptors, BioEssays, 15, 375, 10.1002/bies.950150603 Sporn, 1985, Autocrine growth factors and cancer, Nature, 313, 745, 10.1038/313745a0 Stephens, 2004, Lung cancer: intragenic ERBB2 kinase mutations in tumours, Nature, 431, 525, 10.1038/431525b Threadgill, 1995, Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype, Science, 269, 230, 10.1126/science.7618084 Tokumo, 2005, The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers, Clin. Cancer Res., 11, 1167, 10.1158/1078-0432.1167.11.3 Torrisi, 1999, Eps15 is recruited to the plasma membrane upon epidermal growth factor receptor activation and localizes to components of the endocytic pathway during receptor internalization, Mol. Biol. Cell, 10, 417, 10.1091/mbc.10.2.417 Tropepe, 1997, Transforming growth factor-alpha null and senescent mice show decreased neural progenitor cell proliferation in the forebrain subependyma, J. Neurosci., 17, 7850, 10.1523/JNEUROSCI.17-20-07850.1997 Troyer, 2001, Regulation of mouse mammary gland development and tumorigenesis by the ERBB signaling network, J. Mammary Gland Biol. Neoplasia, 6, 7, 10.1023/A:1009560330359 Troyer, 2001, Growth retardation, duodenal lesions, and aberrant ileum architecture in triple null mice lacking EGF, amphiregulin, and TGF-alpha, Gastroenterology, 121, 68, 10.1053/gast.2001.25478 Tzahar, 1996, A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor, Mol. Cell. Biol., 16, 5276, 10.1128/MCB.16.10.5276 Vassar, 1991, Transgenic mice provide new insights into the role of TGF-alpha during epidermal development and differentiation, Genes Dev., 5, 714, 10.1101/gad.5.5.714 Wallasch, 1995, Heregulin-dependent regulation of HER2/neu oncogenic signaling by heterodimerization with HER3, EMBO J., 14, 4267, 10.1002/j.1460-2075.1995.tb00101.x Watanabe, 1987, Transformation of normal rat kidney (NRK) cells by an infectious retrovirus carrying a synthetic rat type alpha transforming growth factor gene, Proc. Natl. Acad. Sci. U. S. A., 84, 1258, 10.1073/pnas.84.5.1258 Waterman, 1998, Alternative intracellular routing of ErbB receptors may determine signaling potency, J. Biol. Chem., 273, 13819, 10.1074/jbc.273.22.13819 Waterman, 1999, The RING finger of c-Cbl mediates desensitization of the epidermal growth factor receptor, J. Biol. Chem., 274, 22151, 10.1074/jbc.274.32.22151 Wiesen, 1999, Signaling through the stromal epidermal growth factor receptor is necessary for mammary ductal development, Development, 126, 335, 10.1242/dev.126.2.335 Wikstrand, 1998, The class III variant of the epidermal growth factor receptor (EGFRvIII): characterization and utilization as an immunotherapeutic target, J. Neurovirology, 4, 148, 10.3109/13550289809114515 Wiseman, 2005, Coexpression of the type 1 growth factor receptor family members HER-1, HER-2, and HER-3 has a synergistic negative prognostic effect on breast carcinoma survival, Cancer, 103, 1770, 10.1002/cncr.20970 Worthylake, 1999, ErbB-2 amplification inhibits down-regulation and induces constitutive activation of both ErbB-2 and epidermal growth factor receptors, J. Biol. Chem., 274, 8865, 10.1074/jbc.274.13.8865 Xia, 1999, Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members, Clin. Cancer Res., 5, 4164 Xian, 2004, EGF family of growth factors: essential roles and functional redundancy in the nerve system, Front. Biosci., 9, 85, 10.2741/1210 Xian, 2001, Lack of effects of transforming growth factor-alpha gene knockout on peripheral nerve regeneration may result from compensatory mechanisms, Exp. Neurol., 172, 182, 10.1006/exnr.2001.7771 Xie, 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, 766, 10.1210/me.11.12.1766 Xie, 1998, Targeted expression of activated erbB-2 to the epidermis of transgenic mice elicits striking developmental abnormalities in the epidermis and hair follicles, Cell. Growth Differ., 9, 313 Yaffe, 2002, Phosphotyrosine-binding domains in signal transduction, Nat. Rev. Mol. Cell. Biol., 3, 177, 10.1038/nrm759 Yamauchi, 1997, Tyrosine phosphorylation of the EGF receptor by the kinase Jak2 is induced by growth hormone, Nature, 390, 91, 10.1038/36369 Yamauchi, 1997, Prediction of response to antiestrogen therapy in advanced breast cancer patients by pretreatment circulating levels of extracellular domain of the HER-2/c-neu protein, J. Clin. Oncol., 15, 2518, 10.1200/JCO.1997.15.7.2518 Yamauchi, 2000, tyrosine phosphorylation of ErbB-2 via Jak2 by autocrine secretion of prolactin in human breast cancer, J. Biol. Chem., 275, 33937, 10.1074/jbc.M000743200 Yarden, 2001, The EGFR family and its ligands in human cancer. signalling mechanisms and therapeutic opportunities, Eur. J. Cancer, 37, S3, 10.1016/S0959-8049(01)00230-1 Yarden, 2001, Untangling the ErbB signalling network, Nat. Rev. Mol. Cell. Biol., 2, 127, 10.1038/35052073 Zhang, 1996, Transformation of NIH 3T3 cells by HER3 or HER4 receptors requires the presence of HER1 or HER2, J. Biol. Chem., 271, 3884, 10.1074/jbc.271.7.3884 Zhang, 1997, Neuregulin-3 (NRG3): a novel neural tissue-enriched protein that binds and activates ErbB4, Proc. Natl. Acad. Sci. U. S. A., 94, 9562, 10.1073/pnas.94.18.9562