Targeting the epidermal growth factor receptor for therapy of carcinomas

Biochemical Pharmacology

Volumn 51, Issue 9, 1996, Pages 1101-1110

  Davies, Donna E ^a   Chamberlin, Stephen G ^a  

^a SOUTHAMPTON GENERAL HOSPITAL   (United Kingdom)

Author keywords

cancer; epidermal growth factor receptor; growth factors; proliferation; therapy

Indexed keywords

ANTINEOPLASTIC AGENT; CISPLATIN; DOXORUBICIN; EPIDERMAL GROWTH FACTOR; EPIDERMAL GROWTH FACTOR RECEPTOR; RECEPTOR ANTIBODY;

CANCER THERAPY; CARCINOMA; CELL DIVISION; DRUG TARGETING; GENE EXPRESSION; HUMAN; LIGAND BINDING; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; SURVIVAL;

EID: 0029932419     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/0006-2952(95)02232-5     Document Type: Note

References (125)

1. Prigent SA and Lemoine NR, The type 1 (EGFR-related) family of growth factor receptors and their ligands. Prog Growth Factor Res 4: 1-24, 1992.
2. Carpenter G and Wahl MI, The epidermal growth factor family. In: Peptide Growth Factors and Their Receptors (Eds. Sporn MB and Roberts AB), pp. 69-171. Springer, New York, 1991.
3. Tronick SR and Aaronson SA, Growth factors and signal transduction. In: The Molecular Basis of Cancer (Eds. Mendelsohn J, Howley PM, Israel MA and Liotta LA), pp. 117-140. WB Saunders, Philadelphia, 1995.
4. Ullrich A and Schlessinger J, Signal transduction by receptors with tyrosine kinase activity. Cell 61: 203-212, 1990.
5. Gullick WJ, Prevalence of aberrant expression of the epidermal growth factor receptor in human cancers. Br Med Bull 47: 87-98, 1991.
6. Sainsbury JRC, Farndon JR, Sherbet GV and Harris AL, Epidermal growth factor receptors and oestrogen receptors in human breast cancer. Lancet i: 364-366, 1985.
7. Sainsbury JRC, Farndon JR, Needham GK, Malcolm AJ and Harris AL, Epidermal growth-factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet i: 1398-1402, 1987.
8. Sporn MB and Todaro GJ, Autocrine secretion and malignant transformation of cells. New Engl J Med 303: 878-880, 1980.
9. Cook PW, Mattox PA, Keeble WW, Pittelkow MR, Plowman GD, Shoyab M, Adelman JP and Shipley G, A heparin sulphate-regulated human keratinocyte autocrine factor is similar or identical to amphiregulin. Mol Cell Biol 11: 2547-2557, 1991.
10. Coffey RJ Jr, Derynck R, Wilcox JN, Bringman TS, Goustin AS, Moses HL and Pittelkow MR, Production and auto-induction of transforming growth factor-α in human keratinocytes. Nature 328: 817-820, 1987.
11. Hashimoto K, Higashiyama S, Asada H, Hashimura E, Kobayashi T, Sudo K, Nakagawa T, Damm D, Yoshikawa K and Taniguchi N, Heparin-binding epidermal growth factor-like growth factor is an autocrine growth factor for human keratinocytes. J Biol Chem 269: 20060-20066, 1994.
12. Stern DF, Hare DL, Cecchini MA and Weinberg RA, Construction of a novel oncogene based on synthetic sequences encoding epidermal growth factor. Science 235: 321-324, 1987.
13. Finzi E, Fleming T and Pierce JH, Retroviral expression of transforming growth factor-alpha does not transform fibroblasts or keratinocytes. J Invest Dermatol 95: 382-387, 1990.
14. Di Marco E, Pierce JH, Fleming TP, Kraus MH, Molloy CJ, Aaronson SA and Di Fiore PP, Autocrine interaction between TGF alpha and the EGF-receptor: Quantitative requirements for induction of the malignant phenotype. Oncogene 4: 831-838, 1989.
15. Derynck R, Goeddel DV, Ullrich A, Gutterman JU, William RD, Bringman TS and Berger WH, Synthesis of messenger RNAs for transforming growth factor α and β and the epidermal growth factor receptor by human tumors. Cancer Res 47: 707-712, 1987.
16. Ennis BW, Valverius EM, Bates SE, Lippman ME, Bellot F, Kris R, Schlessinger J, Masui H, Goldenberg A, Mendelsohn J and Dickson RB, Anti-epidermal growth factor receptor antibodies inhibit the autocrine-stimulated growth of MDA-468 human breast cancer cells. Mol Endocrinol 3: 1830-1838, 1989.
17. Modjtahedi H, Styles J and Dean C, The growth response of human tumour cell lines expressing the EGF receptor to treatment with EGF and/or Mabs that block ligand binding. Int J Oncol 3: 237-243, 1993.
18. Messing EM, Clinical implications of the expression of epidermal growth factor receptors in human transitional cell carcinomas. Cancer Res 50: 2530-2537, 1990.
19. Aida S, Tamai S, Sekiguchi S and Shimizu N, Distribution of epidermal growth factor and epidermal growth factor receptor in human lung: Immunohistochemical and immunoelectron-microscopic studies. Respiration 61: 161-166, 1994.
20. Menard D and Pothier P, Radioautographic localization of epidermal growth factor receptors in human fetal gut. Gastroenterology 101: 640-649, 1991.
21. Decker SJ, Transmembrane signalling by epidermal growth factor receptors lacking autophosphorylation sites. J Biol Chem 268: 9176-9179, 1993.
22. Chen P, Xie H, Sekar MC, Gupta K and Wells A, Epidermal growth factor receptor-mediated cell motility: Phospholipase C activity is required, but mitogen activated-protein kinase activity is not sufficient for induced cell movement. J Cell Biol 127: 847-857, 1994.
23. Mattay MA, Thiery JP, Lafont F, Stampfer MF and Boyer B, Transient effect of epidermal growth factor on the motility of an immortalized mammary epithelial cell line. J Cell Sci 106: 869-878, 1993.
24. Blay J and Brown KD, Epidermal growth factor promotes the chemotactic migration of cultured rat intestinal epithelial cells. J Cell Physiol 124: 107-112, 1985.
25. Li Y, Bhargava A, Jin JL, Rosen EM and Goldberg ID, Effect of hepatocyte growth factor/scatter factor and other growth factors on motility and morphology of non-tumorigenic and tumor cells. In Vitro Cell Dev Biol 30A: 105-110, 1994.
26. Shibamoto S, Hayakawa M, Takeuchi K, Hori T, Oku N, Miyazawa K, Kitamura N, Takeichi M and Ito F, Tyrosine phosphorylation of β-catenin and plakoglobin enhanced by hepatocyte growth factor and epidermal growth factor in human carcinoma cells. Cell Adhesion Commun 1: 295-305, 1994.
27. Chen JD, Kim JP, Zhang K, Sarret Y, Wynn KC, Kramer RH and Woodley DT, Epidermal growth factor (EGF) promotes human keratinocyte locomotion on collagen by increasing the α2 integrin subunit. Exp Cell Res 209: 216-223, 1993.
28. Neal DE, Bennett MK, Hall RR, Marsh C, Abel PD, Sainsbury JRC and Harris AL, Epidermal growth factor receptors in human bladder cancer: Comparison of invasive and superficial tumours. Lancet i: 366-368, 1985.
29. Mullins DE and Rifkin DB, Induction of proteases and protease inhibitors by growth factors. In: Peptide Growth Factors and Their Receptors II (Eds. Sporn MB and Roberts AB), pp. 481-507. Springer, New York, 1990.
30. Shima I, Sasaguri Y, Kusukawa J, Nakano R, Yamana H, Fujita H, Kakegawa T and Morimatsu M, Production of matrix metalloproteinase 9 (92-kDa gelatinase) by human oesophageal squamous cell carcinoma in response to epidermal growth factor. Br J Cancer 67: 721-727, 1993.
31. Gavrilovic J, Moens G, Thiery JP and Jouanneau J, Expression of transfected transforming growth factor α induces a motile fibroblastic phenotype with extracellular matrix-degrading potential in a rat bladder carcinoma cell line. Cell Regul 1: 1003-1014, 1990.
32. Hayashido Y, Shirasuna K and Matsuya T, Effect of epidermal growth factor on invasion of human squamous cell carcinoma cells into collagen gels. Cancer J 4: 257-261, 1991.
33. 2-integrin with a concomitant decrease in E-cadherin in GP5d colon carcinoma cells. Br J Cancer 71(Suppl XXIV): 30, 1995.
34. Gottesman MM and Pastan I, Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem 62: 385-427, 1993.
35. Geier A, Hemi R, Haimsohn M, Berry R, Malik Z and Karasik A, Epidermal growth factor and insulin-like growth factor-1 protect MDA-231 cells from death induced by actinomycin D: The involvement of growth factors in drug resistance. In Vitro Cell Dev Biol 30A: 336-343, 1994.
36. Dickstein B, Valverius EM, Wosikowski K, Saceda M, Pearson JW, Martin MB and Bates SE, Increased epidermal growth factor receptor in an estrogen-responsive, adriamycin-resistant MCF-7 cell line. J Cell Physiol 157: 110-118, 1993.
37. Meyers MB, Shen WPV, Spengler WPA, Ciccarone V, O'Brien JP, Donner DB, Furth ME and Biedler JL, Increased epidermal growth factor receptor in multidrug resistant neuroblastoma cells. J Cell Biochem 38: 87-97, 1988.
38. Zuckier G and Tritton TR, Adriamycin causes upregulation of epidermal growth factor receptors in actively growing cells. Exp Cell Res 148: 155-161, 1983.
39. Meyers MB, Yu P and Mendelsohn J, Crosstalk between epidermal growth factor receptor and P-glycoprotein in actinomycin D-resistant Chinese hamster lung cells. Biochem Pharmacol 46: 1841-1848, 1993.
40. Folkman J, Tumor angiogenesis. In: The Molecular Basis of Cancer (Eds. Mendelsohn J, Howley PM, Israel MA and Liotta LA), pp. 206-232. WB Saunders, Philadelphia, 1995.
41. Schreiber AB, Winkler ME and Derynck R, Transforming growth factor-α: A more potent angiogenic mediator than epidermal growth factor. Science 232: 1250-1253, 1986.
42. Colige AC, Lambert CA, Nusgens BV and Lapière CM, Effect of cell-cell and cell-matrix interactions on the response of fibroblasts to epidermal growth factor in vitro. Biochem J 285: 215-221, 1992.
43. Seebacher T, Manske M, Kornblihtt AR and Bade EG, Cellular fibronectin is induced by epidermal growth factor, but not by dexamethasone or cyclic AMP in rat liver epithelial cells. FEBS Lett 239: 113-116, 1988.
44. Le PT, Lazorick S, Whichard LP, Haynes BF and Singer KH, Regulation of cytokine production in the human thymus: Epidermal growth factor and transforming growth factor α regulate mRNA levels of interleukin 1α (IL-1α), IL-β, and IL-6 in human thymic epithelial cells at a post-transcriptional level. J Exp Med 174: 1147-1157, 1991.
45. Alexander P, The role of the host in facilitating and controlling the development and spread of cancer. In: Biology of Carcinogenesis (Eds. Waring MJ and Ponder B), pp. 191-221. M.T.P. Press, Lancaster, 1987.
46. Murphy P, Alexander P, Senior PV, Fleming J, Kirkham N and Taylor I, Mechanisms of organ selective tumour-growth of bloodborne cancer cells. Br J Cancer 57: 19-31, 1988.
47. Skipper D, Jeffrey MJ, Cooper AJ, Taylor I and Alexander P, Preferential growth of bloodborne cancer cells in colonie anastomoses. Br J Cancer 57: 564-568, 1988.
48. Kurachi H, Okamoto S and Oka T, Evidence for the involvement of the submandibular gland epidermal growth factor in mouse mammary tumorigenesis. Proc Natl Acad Sci USA 82: 5940-5943, 1985.
49. Tsutsumi O, Tsutsumi T and Oka T, Importance of epidermal growth factor in implantation and growth of mouse mammary tumour in female nude mice. Cancer Res 47: 4651-4653, 1987.
50. Inui T, Tsubura A and Morii S, Incidence of precancerous foci of mammary glands and growth rate of transplantable mammary cancers in sialoadenectomized mice. J Natl Cancer Inst 81: 660-663, 1989.
51. Davies DE, Farmer S, White J, Senior PV, Warnes SL and Alexander P, Contribution of host derived growth factors to in vivo growth of a transplantable murine mammary carcinoma. Br J Cancer 70: 263-269, 1994.
52. Campbell ID, Cooke RM, Baron M, Harvey TS and Tappin MJ, The solution structures of epidermal growth factor and transforming growth factor alpha. Prog Growth Factor Res 1: 13-22, 1989.
53. Szyperski T, Güntert P, Stone SR and Wüthrich K, Nuclear magnetic resonance solution structure of hirudin(1-51) and comparison with corresponding three-dimensional structures determined using the complete 65-residue hirudin polvpeptide chain. J Mol Biol 228: 1193-1205, 1992.
54. Taylor JM, Mitchell WM and Cohen S, Epidermal growth factor. Physical and chemical properties. J Biol Chem 247: 5928-5934, 1972.
55. DeLarco JE, Reynolds R, Carlberg K, Engle C and Todaro GJ, Sarcoma growth factor from mouse sarcoma virus-transformed cells. Purification by binding and elution from epidermal growth factor receptor rich cells. J Biol Chem 255: 3685-3690, 1980.
56. Higashiyama S, Lau K, Besner GE, Abraham JA and Klagsbrun M, Structure of heparin-binding EGF-like growth factor. J Biol Chem 267: 6205-6212, 1991.
57. Shoyab M, McDonald VL, Bradley JG and Todaro GJ, 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 USA 85: 6528-6532, 1988.
58. Johnson GR and Wong L, Heparin sulfate is essential to amphiregulin-induced mitogenic signaling by the epidermal growth factor receptor. J Biol Chem 269: 27149-27154, 1994.
59. Besner GE, Whelton D, Crissman-Combs MA, Steffen CL, Kim GY and Brigstock DR, Modulation of heparin-binding EGF-like growth factor (HB-EGF) with the epidermal growth factor receptor: Modulation by heparin, heparinase, or synthetic heparin-binding HB-EGF fragments. Growth Factors 7: 289-296, 1992.
60. Shing Y, Christofori G, Hanahan D, Ono Y, Sasada R, Igarashi K and Folkman J, Betacellulin: A mitogen from pancreatic β-cell tumors. Science 259: 1604-1607, 1993.
61. Shoyab M, Plowman GD, McDonald VL, Bradley JG and Todaro GJ, Structure and function of human amphiregulin: A member of the epidermal growth factor family. Science 243: 1074-1076, 1989.
62. Solic N and Davies DE, Differential effects of epidermal growth factor and amphiregulin on growth and morphology of two colon carcinoma cell lines. Eur J Clin Invest 25 (Suppl 2): pA53, 1995.
63. Adam R, Drummond DR, Solic N, Holt SJ, Sharma RP, Chamberlin SG and Davies DE, Modulation of the receptor binding affinity of amphiregulin by modification of its carboxyl terminal tail. Biochim Biophys Acta 1266: 83-90, 1995.
64. Normanno N, Qi C-F, Gullick WJ, Persico G, Yarden Y, Wen D, Plowman G, Kenney N, Johnson G, Kim N, Brandt R, Martinez-Lacaci I, Dickson RB and Salomon DS, Expression of amphiregulin, cripto-1 and heregulin alpha in breast cancer cells. Int J Oncol 2: 903-911, 1993.
65. LeJeune S, Leek R, Horak E, Plowman G, Greenall M and Harris AL, Amphiregulin, epidermal growth factor receptor, and estrogen receptor status in human primary breast cancer. Cancer Res 53: 3597-3602, 1993.
66. Saeki T, Stromberg K, Qi C-F, Gullick WJ, Tahara E, Normanno N, Ciardiello F, Kenney N, Johnson G and Salomon DS, Differential immunohistochemical detection of amphiregulin and cripto in human normal colon and colorectal tumours. Cancer Res 52: 3467-3473, 1992.
67. Cook PW, Pittelkow MR, Keeble WW, Graves-Deal R, Coffey RJ and Shipley GD, Amphiregulin messenger RNA is elevated in psoriatic epidermis and gastrointestinal carcinomas. Cancer Res 52: 3224-3227, 1992.
68. Johnson GR, Saeki T, Auersperg N, Gordon AW, Shoyab M, Salomon DS and Stromberg K, Response to and expression of amphiregulin by ovarian carcinoma and normal ovarian surface epithelial cells: Nuclear localization of endogenous amphiregulin. Biochem Biophys Res Commun 180: 481-488, 1991.
69. Ebert M, Yokoyama M, Kobrin MS, Fruess H, Lopez ME, Büchler MW, Johnson GR and Korc M, Induction and expression of amphiregulin in human pancreatic cancer. Cancer Res 54: 3959-3962, 1994.
70. Yanai S, Sugiyama Y, Iga T, Fuwa T and Hanano M, Kinetic analysis of the downregulation of epidermal growth factor receptors in rats in vivo. Am J Physiol 258: C593-C598, 1990.
71. Liberman TA, Nusbaum HR, Razon N, Kris R, Lax I, Soreq H, Whittle N, Waterfield MD, Ullrich A and Schlessinger J, Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 313: 144-147, 1985.
72. Yamazaki H, Ohba Y, Tamaoki N and Shibuya M, A deletion mutation within the ligand binding domain is responsible for activation of epidermal growth factor gene in human brain tumors. Jpn J Cancer Res 81: 773-779, 1990.
73. Garcia de Palazzo IE, Adams GP, Sundareshan P, Wong AJ, Testa J, Bigner DD and Weiner LM, Expression of mutated epidermal growth factor receptor by non-small cell lung carcinomas. Cancer Res 53: 3217-3220, 1993.
74. Kreitman RJ, Fitzgerald D and Pastan I, Targeting growth factor receptors with fusion toxins. Int J Immunopharmacol 14: 465-472, 1992.
75. Mesri EA, Kreitman RJ, Fu Y-M, Epstein SE and Pastan I, Heparin-binding transforming growth factor α-Pseudomonas exotoxin A. A heparin sulfate-modulated recombinant toxin cytotoxic to cancer cells and proliferating smooth muscle cells. J Biol Chem 268: 4853-4862, 1993.
76. Kirk J, Carmichael J, Stratford IJ and Harris AL, Selective toxicity of TGF-α-PE40 to EGFR-positive cell lines: Selective protection of low EGFR-expressing cell lines by EGF. Br J Cancer 69: 988-994, 1994.
77. Kameyama S, Kawamata H, Pastan I and Oyasu R, Cytotoxic effect of a fusion protein from transforming growth factor α and Pseudomonas exotoxin on rat and human bladder carcinoma cells in vitro. J Cancer Res Clin Oncol 120: 507-512, 1994.
78. Pai LH, Gallo MG, FitzGerald DJ and Pastan I, Antitumor activity of a transforming growth factor α-Pseudomonas exotoxin fusion protein (TGF-α-PE40). Cancer Res 51: 2808-2812, 1991.
79. Phillips PC, Levow C, Catterall M, Colvin M, Pastan I and Brem H, Transforming growth factor-α-Pseudomonas exotoxin fusion protein (TGF-α-PE38) treatment of subcutaneous and intracranial human glioma and medulloblastoma xenografts in athymic mice. Cancer Res 54: 1008-1015, 1994.
80. Theuer CP, FitzGerald DJ and Pastan I, A recombinant form of Pseudomonas exotoxin A containing transforming growth factor alpha near its carboxyl terminus for the treatment of bladder cancer. J Urol 149: 1626-1632, 1993.
81. Modjtahedi H and Dean C, The receptor for EGF and its ligands: Expression, prognostic value and target for therapy in cancer. Int J Oncol 4: 277-296, 1994.
82. Masui H, Kawamoto T, Sato JD, Wolf B, Sato G and Mendelsohn J, Growth inhibition of human tumor cells in athymic mice by anti-epidermal growth factor receptor monoclonal antibodies. Cancer Res 44: 1002-1007, 1984.
83. Masui H, Moroyama T and Mendelsohn J, Mechanism of antitumor activity in mice for anti-epidermal growth factor receptor monoclonal antibodies with different isotypes. Cancer Res 46: 5592-5598, 1986.
84. Schnürch H-G, Stegmüller M, Vering A, Beckmann MW and Bender HG, Growth inhibition of xenotransplanted human carcinomas by a monoclonal antibody directed against the epidermal growth factor receptor. Eur J Cancer 30A: 491-496, 1994.
85. Modjtahedi H, Eccles S, Box G, Styles J and Dean C, Immunotherapy of human tumour xenografts overexpressing the EGF receptor with rat antibodies that block growth factor-receptor interaction. Br J Cancer 67: 254-261, 1993.
86. Fan Z, Baselga J, Masui H and Mendelsohn J, Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established A431 cell xenografts. Cancer Res 53: 4637-4642, 1993.
87. Baselga J, Norton L, Masui H, Pandiella A, Coplan K, Miller WH and Mendelsohn J, Antitumour effects of doxorubicin in combination with anti-epidermal growth factor receptor monoclonal antibodies. J Natl Cancer Inst 85: 1327-1333, 1993.
88. Aboud-Pirak E, Hurwitz E, Bellot F, Schlessinger J and Sela M, Inhibition of human tumor growth in nude mice by conjugate of doxorubicin with monoclonal antibodies to epidermal growth factor receptor. Proc Natl Acad Sci USA 86: 3778-3781, 1989.
89. Morelli D, Sardini A, Villa E, Villa ML, Menard S, Colnaghi MI and Balsari A, Modulation of drug induced cytotoxicity by a bispecific monoclonal antibody that recognizes the epidermal growth factor receptor and doxorubicin. Cancer Immunol Immunother 38: 171-177, 1994.
90. Maloney DG, Levy R and Campbell MJ, Monoclonal antibody therapy. In: The Molecular Basis of Cancer (Eds. Mendelsohn J, Howley PM, Israel MA and Liotta LA), pp. 460-510. WB Saunders, Philadelphia, 1995.
91. Divgi CR, Welt S, Kris M, Real FX, Yeh SDJ, Gralla R, Merchant B, Schweighart S, Unger M, Larson SM and Mendelsohn J, Phase I and imaging trial of indium 111-labelled anti-epidermal growth factor receptor monoclonal antibody 225 in patients with squamous cell lung cancer. J Natl Cancer Inst 83: 97-104, 1991.
92. Dadparvar S, Krishna L, Miyamoto C, Brady LW, Brown SJ, Bender H, Slizofski WJ, Eshleman J, Chevres A and Woo DV, Indium-111-labeled anti-EGFr-425 scintigraphy in the detection of malignant gliomas. Cancer 73: 884-889, 1994.
93. Gibbs JB and Oliff A, Pharmaceutical research in molecular oncology. Cell 79: 193-198, 1994.
94. Silvennoinen O, Schindler C, Schlessinger J and Levy DE, Ras-independent growth factor signaling by transcription factor tyrosine phosphorylation. Science 261: 1736-1739, 1993.
95. ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor. Cell 73: 611-620, 1993.
96. Gotoh N, Tojo A, Muyoya K, Hashimoto Y, Hattori S, Nakamura S, Takenawa T, Yazaki Y and Shibuya M, Epidermal growth factor-receptor mutant lacking the autophosphorylation sites induces phosphorylation of She protein and Shc-Grb/ASH association and retains mitogenic activity. Proc Natl Acad Sci USA 91: 167-171, 1994.
97. Schally AV, Radulovic S and Comaru-Schally AM, Experimental and clinical studies in hormone-dependent cancers. In: Endocrine Tumors (Eds. Mazzaferri EL and Samaan NA), pp. 49-73. Blackwell Scientific Publications, Oxford, U.K., 1993.
98. Mann GB, Fowler KJ, Gabriel A, Nice EC, Williams RL and Dunn AR, Mice with a null mutation of the TGFα gene have abnormal skin architecture, wavy hair, and curly whiskers and often develop corneal inflammation. Cell 73: 249-261, 1993.
99. Levitski A and Gazit A, Tyrosine kinase inhibition: An approach to drug development. Science 267: 1782-1787, 1995.
100. Buchdunger E, Trinks U, Mett H, Regenass U, Muller M, Meyer T, McGlynn E, Pinna LA, Traxler P and Lydon NB, 4,5-Dianilinophthalimimide: A protein-tyrosine kinase inhibitor with selectivity for the epidermal growth factor receptor signal transduction pathway and potent in vivo antitumor activity. Proc Natl Acad Ssi USA 91: 2334-2338, 1994.
101. Fry DW, Kraker AJ, McMichael A, Ambroso LA, Nelson JM, Leopold WR, Connors RW and Bridges A, A specific inhibitor of the epidermal growth factor receptor tyrosine kinase. Science 265: 1093-1095, 1994.
102. Winkler ME, O'Connor L, Winget M and Fendly B, Epidermal growth factor and transforming growth factor α bind differently to the epidermal growth factor receptor. Biochemistry 28: 6373-6378, 1989.
103. Campion SR and Niyogi SK, Interaction of epidermal growth factor with its receptor. Prog Nucleic Acid Res Mol Biol 49: 353-383, 1995.
104. Richter A, Conlan JW, Ward ME, Chamberlin SG, Alexander P, Richards NGJ and Davies DE, Multidomain binding of transforming growth factor α to the epidermal growth factor receptor. Biochemistry 31: 9546-9554, 1992.
105. Engler DA, Campion SR, Hauser MR, Cook JS and Niyogi SK, Critical functional requirement for the guanidinium group of the arginine 41 side chain of human epidermal growth factor as revealed by mutagenic inactivation and chemical reactivation. J Biol Chem 267: 2274-2281, 1992.
106. Matsunami RK, Yette ML, Stevens A and Niyogi SK, Mutational analysis of leucine 47 in human epidermal growth factor. J Cell Biochem 46: 242-249, 1991.
107. Richter A, Drummond DR, MacGarvie J, Puddicombe SM, Chamberlin SG and Davies DE, Contribution of the transforming growth factor α B-loop β-sheet to binding and activation of the epidermal growth factor receptor. J Biol Chem 270: 1612-1616, 1995.
108. Clackson T and Wells JA, A hot spot of binding energy in a hormone-receptor interface. Science 267: 383-386, 1995.
109. Komoriya A, Hortsch M, Meyers C, Smith M, Kanety H and Schlessinger J, Biologically active fragments of epidermal growth factor: Localization of a major receptor-binding region. Proc Natl Acad Sci USA 81: 1351-1355, 1984.
110. Darlak K, Franklin G, Woost P, Sonnenfeld E, Twardzik D, Spatola A and Schultz G, Assessment of biological activity of synthetic fragments of transforming growth factor-alpha. J Cell Biochem 36: 341-352, 1988.
111. Han K, Ferretti J, Niu C, Lokeshwar V, Clarke R and Katz D, Conformational and receptor binding properties of human EGF and TGF-α second loop fragments. J Mol Recognit 1: 116-123, 1988.
112. Katsuura M and Tanaka S, Topographic analysis of human epidermal growth factor by monospecific antibodies and synthetic peptides. J Biochem (Tokyo) 106: 87-92, 1989.
113. Nelson J, Stewart R, McGivern M, Bailie JR, Walker B, Murphy RF and Wilson DJ, Synthetic murine epidermal growth factor sequence 20-31 is mitogenic and angiogenic. Carcinogenesis 12: 1823-1829, 1991.
114. Chamberlin SG, Sargood KJ, Richter A, Mellor JM, Anderson DW, Richards NGJ, Turner DL, Sharma RP, Alexander P and Davies DE, Constrained peptide analogues of transforming growth factor alpha residues [21-32] are mitogenically active: Use of proline mimetics to enhance biological potency. J Biol Chem 270:21062-21067, 1995.
115. Kenan DJ, Tsai DE and Keene JD, Exploring molecular diversity with combinatorial shape libraries. Trends Biochem Sci 19: 57-64, 1994.
116. Bargmann CI and Weinberg RA, Oncogenic activation of the neu-encoded receptor protein by point mutation and deletion. EMBO J 7: 2043-2052, 1988.
117. Kashles O, Szapary D, Bellot F, Ullrich A, Schlessinger J and Schmidt A, Ligand-induced stimulation of epidermal growth factor receptor mutants with altered transmembrane regions. Proc Natl Acad Sci USA 85: 9567-9571, 1988.
118. Kashles O, Yarden Y, Fischer R, Ullrich A and Schlessinger J, A dominant negative mutation suppresses the function of normal epidermal growth factor receptors by heterodimerization. Mol Cell Biol 11: 1454-1463, 1991.
119. Lemmon MA and Schlessinger J, Regulation of signal transduction and signal diversity by receptor oligomerization. Trends Biochem Sci 19: 459-463, 1994.
120. Carraway KL III and Cantley LC, A neu acquaintance for erbB3 and erbB4: A role for receptor heterodimerization in growth signaling. Cell 78: 5-8, 1994.
121. neu protein and EGF receptor modulates EGF receptor function. Cell 61: 1339-1347, 1990.
122. Karunagaran D, Tzahar E, Liu N, Wen D and Yarden Y, Neu differentiation factor inhibits EGF binding. A model for trans-regulation within the ErbB family of receptor tyrosine kinases. J Biol Chem 270: 9982-9990, 1995.
123. Marshall CJ, Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation. Cell 80: 179-185, 1995.
124. Rosdy M, Opposite effects of EGF on involucrin accumulation of A431 keratinocytes and a variant which is not growth-arrested by EGF. In Vitro Cell Dev Biol 24: 1127-1132, 1988.
125. Modjtahedi H, Eccles S, Sandle J, Box G, Titley J and Dean C, Differentiation or immune destruction: Two pathways for therapy of squamous cell carcinomas with antibodies to the epidermal growth factor receptor. Cancer Res 54: 1695-1701, 1994.