Ovarian Cancer pp 203-226 | Cite as

Activated Epidermal Growth Factor Receptor in Ovarian Cancer

  • Laurie G. HudsonEmail author
  • Reema Zeineldin
  • Melina Silberberg
  • M. Sharon Stack
Part of the Cancer Treatment and Research book series (CTAR, volume 149)

Background: The Epidermal Growth Factor Receptor

Growth factor receptors direct numerous cellular functions and behavior including cell proliferation and survival, apoptosis, differentiation, and migration. The receptor tyrosine kinase (RTK) family of growth factor receptors includes the epidermal growth factor (EGF) receptor subfamily (also known as the ErbB or type I RTKs). 1, 2, 3, 4, 5 The ErbB family includes four ErbB proteins: ErbB-1 (EGF receptor), ErbB2, ErbB3, and ErbB4. These structurally related, single membrane spanning receptors consist of an extracellular ligand-binding domain, a transmembrane domain, a juxtamembrane domain, the catalytic tyrosine kinase domain, and a C-terminal tail containing multiple tyrosine residues (Fig. 10.1). Ligand binding promotes EGF receptor homo- and heterodimerization with ErbB family members, activation of the intracellular tyrosine kinase domain, and phosphorylation of specific tyrosine residues of the receptor cytoplasmic domain. This...


Ovarian Cancer Epidermal Growth Factor Receptor Ovarian Tumor Epidermal Growth Factor Receptor Expression Ovarian Surface Epithelium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by National Institutes of Health grants R01 CA90492 (L.G.H.), R01 CA86984 (M.S.S.), and R01 CA109545 (M.S.S. and L.G.H.).


  1. 1.
    Bazley LA, Gullick WJ. The epidermal growth factor receptor family. Endocr Relat Cancer. 2005 Jul;12(Suppl 1):S17–S27.PubMedGoogle Scholar
  2. 2.
    Linggi B, Carpenter G. ErbB receptors: new insights on mechanisms and biology. Trends Cell Biol. 2006 Dec;16(12):649–656.PubMedGoogle Scholar
  3. 3.
    Citri A, Yarden Y. EGF-ERBB signaling: towards the systems level. Nat Rev Mol Cell Biol. 2006 Jul;7(7):505–516.PubMedGoogle Scholar
  4. 4.
    Wieduwilt MJ, Moasser MM. The epidermal growth factor receptor family: biology driving targeted therapeutics. Cell Mol Life Sci. 2008 May;65(10):1566–1584.PubMedGoogle Scholar
  5. 5.
    Lafky JM, Wilken JA, Baron AT, Maihle NJ. Clinical implications of the ErbB/epidermal growth factor (EGF) receptor family and its ligands in ovarian cancer. Biochim Biophys Acta. 2008 Apr;1785(2):232–265.PubMedGoogle Scholar
  6. 6.
    Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer. 2005 May;5(5):341–354. Review. Erratum in: Nat Rev Cancer. 2005 Jul;5(7):580.PubMedGoogle Scholar
  7. 7.
    Mendelsohn J, Baselga J. Epidermal growth factor receptor targeting in cancer. Semin Oncol. 2006 Aug;33(4):369–385.PubMedGoogle Scholar
  8. 8.
    Normanno N, De Luca A, Bianco C, et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene. 2006 Jan 17;366(1):2–16.PubMedGoogle Scholar
  9. 9.
    Sibilia M, Kroismayr R, Lichtenberger BM, et al. The epidermal growth factor receptor: from development to tumorigenesis. Differentiation. 2007 Nov;75(9):770–787.PubMedGoogle Scholar
  10. 10.
    Schneider MR, Werner S, Paus R, Wolf E. Beyond wavy hairs: the epidermal growth factor receptor and its ligands in skin biology and pathology. Am J Pathol. 2008 Jul;173(1):14–24.PubMedGoogle Scholar
  11. 11.
    Harris RC, Chung E, Coffey RJ. EGF receptor ligands. Exp Cell Res. 2003 Mar 10;284(1):2–13.PubMedGoogle Scholar
  12. 12.
    Singh AB, Harris RC. Autocrine, paracrine and juxtacrine signaling by EGFR ligands. Cell Signal. 2005 Oct;17(10):1183–1193.PubMedGoogle Scholar
  13. 13.
    Amit I, Wides R, Yarden Y. Evolvable signaling networks of receptor tyrosine kinases: relevance of robustness to malignancy and to cancer therapy. Mol Syst Biol. 2007;3:151.PubMedGoogle Scholar
  14. 14.
    Downward J, Yarden Y, Mayes E, et al. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature. 1984 Feb 9–15;307(5951):521–527.PubMedGoogle Scholar
  15. 15.
    Zhang H, Berezov A, Wang Q, et al. ErbB receptors: from oncogenes to targeted cancer therapies. J Clin Invest. 2007 Aug;117(8):2051–2058.PubMedGoogle Scholar
  16. 16.
    Bublil EM, Yarden Y. The EGF receptor family: spearheading a merger of signaling and therapeutics. Curr Opin Cell Biol. 2007 Apr;19(2):124–134.PubMedGoogle Scholar
  17. 17.
    Johnston JB, Navaratnam S, Pitz MW, et al. Targeting the EGFR pathway for cancer therapy. Curr Med Chem. 2006;13(29):3483–3492.PubMedGoogle Scholar
  18. 18.
    Ciardiello F, Tortora G. EGFR antagonists in cancer treatment. N Engl J Med. 2008 Mar 13;358(11):1160–1174.PubMedGoogle Scholar
  19. 19.
    Zandi R, Larsen AB, Andersen P, et al. Mechanisms for oncogenic activation of the epidermal growth factor receptor. Cell Signal. 2007 Oct;19(10):2013–2023.PubMedGoogle Scholar
  20. 20.
    Riese D, Gallo R, Settleman J. Mutational activation of ErbB family receptor tyrosine kinases: insights into mechanisms of signal transduction and tumorigenesis. Bioessays. 2007 Jun;29(6):558–565.PubMedGoogle Scholar
  21. 21.
    Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000 Jan 7;100(1):57–70.PubMedGoogle Scholar
  22. 22.
    Condeelis J, Singer RH, Segall JE. The great escape: when cancer cells hijack the genes for chemotaxis and motility. Annu Rev Cell Dev Biol. 2005;21:695–718.PubMedGoogle Scholar
  23. 23.
    Auersperg N, Wong AS, Choi KC, et al. Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr Rev. 2001 Apr;22(2):255–288.PubMedGoogle Scholar
  24. 24.
    Conti M, Hsieh M, Park JY, et al. Role of the epidermal growth factor network in ovarian follicles. Mol Endocrinol. 2006 Apr;20(4):715–723.PubMedGoogle Scholar
  25. 25.
    Ben-Ami I, Freimann S, Armon L, et al. Novel function of ovarian growth factors: combined studies by DNA microarray, biochemical and physiological approaches. Mol Hum Reprod. 2006 Jul;12(7):413–419.PubMedGoogle Scholar
  26. 26.
    Choi KC, Auersperg N. The ovarian surface epithelium: simple source of a complex disease. Minerva Ginecol. 2003 Aug;55(4):297–314.PubMedGoogle Scholar
  27. 27.
    Naora H. The heterogeneity of epithelial ovarian cancers: reconciling old and new paradigms. Expert Rev Mol Med. 2007 May 4;9(13):1–12.PubMedGoogle Scholar
  28. 28.
    Wong AS, Auersperg N. Normal ovarian surface epithelium. Cancer Treat Res. 2002;107:161–183.PubMedGoogle Scholar
  29. 29.
    Lassus H, Sihto H, Leminen A, et al. Gene amplification, mutation, and protein expression of EGFR and mutations of ERBB2 in serous ovarian carcinoma. J Mol Med. 2006 Aug;84(8):671–681.PubMedGoogle Scholar
  30. 30.
    Stadlmann S, Gueth U, Reiser U, et al. Epithelial growth factor receptor status in primary and recurrent ovarian cancer. Mod Pathol. 2006 Apr;19(4):607–610.PubMedGoogle Scholar
  31. 31.
    Dimova I, Zaharieva B, Raitcheva S, et al. Tissue microarray analysis of EGFR and erbB2 copy number changes in ovarian tumors. Int J Gynecol Cancer. 2006 Jan–Feb;16(1):145–151.PubMedGoogle Scholar
  32. 32.
    Ilekis JV, Connor JP, Prins GS, et al. Expression of epidermal growth factor and androgen receptors in ovarian cancer. Gynecol Oncol. 1997;66:250–254.PubMedGoogle Scholar
  33. 33.
    Baekelandt M, Kristensen GB, Trope CG, et al. Epidermal growth factor receptor expression has no independent prognostic significance in advanced ovarian cancer. Anticancer Res. 1999;19:4469–4474.PubMedGoogle Scholar
  34. 34.
    Skirnisdottir I, Sorbe B, Seidal T. The growth factor receptors HER-2/neu and EGFR, their relationship, and their effects on the prognosis in early stage (FIGO I-II) epithelial ovarian carcinoma. Int J Gynecol Cancer. 2001;11:119–129.PubMedGoogle Scholar
  35. 35.
    Marozkina NV, Stiefel SM, Frierson HF Jr, et al. MMTV-EGF receptor transgene promotes preneoplastic conversion of multiple steroid hormone-responsive tissues. J Cell Biochem. 2008 Apr 15;103(6):2010–2018.PubMedGoogle Scholar
  36. 36.
    Stromberg K, Johnson G, O'Connor D, et al. Frequent immunohistochemical detection of EGF supergene family members in ovarian carcinogenesis. Int J Gynecol Pathol. 1994;13(4):342–347.PubMedGoogle Scholar
  37. 37.
    Niikura H, Sasano H, Sato S, et al. Expression of epidermal growth factor-related proteins and epidermal growth factor receptor in common epithelial ovarian tumors. Int J Gynecol Pathol. 1997;16:60–68.PubMedGoogle Scholar
  38. 38.
    Feldkamper M, Enderle-Schmitt U, Hackenberg R, et al. Urinary excretion of growth factors in patients with ovarian cancer. Eur J Cancer. 1994;30A:1851–1858.PubMedGoogle Scholar
  39. 39.
    Ridderheim M, Cajander S, Tavelin B, et al. EGF/TGF-α and progesterone in urine of ovarian cancer patients. Anticancer Res. 1994;14:2119–2123.PubMedGoogle Scholar
  40. 40.
    Shah NG, Bhatavdekar JM, Doctor SS, et al. Circulating epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) in patients with epithelial ovarian carcinoma. Neoplasma. 1994;41:241–243.PubMedGoogle Scholar
  41. 41.
    Tanaka Y, Miyamoto S, Suzuki SO, et al. Clinical significance of heparin-binding epidermal growth factor-like growth factor and a disintegrin and metalloprotease 17 expression in human ovarian cancer. Clin Cancer Res. 2005 Jul 1;11(13):4783–4792.PubMedGoogle Scholar
  42. 42.
    Yotsumoto F, Yagi H, Suzuki SO, et al. Validation of HB-EGF and amphiregulin as targets for human cancer therapy. Biochem Biophys Res Commun. 2008 Jan 18;365(3):555–561.PubMedGoogle Scholar
  43. 43.
    Miyamoto S, Hirata M, Yamazaki A, et al. Heparin-binding EGF-like growth factor is a promising target for ovarian cancer therapy. Cancer Res. 2004 Aug 15;64(16):5720–5727.PubMedGoogle Scholar
  44. 44.
    Casamassimi A, De Luca A, Agrawal S, et al. EGF-related antisense oligonucleotides inhibit the proliferation of human ovarian carcinoma cells. Ann Oncol. 2000 Mar;11(3):319–325.PubMedGoogle Scholar
  45. 45.
    Psyrri A, Kassar M, Yu Z, et al. Effect of epidermal growth factor receptor expression level on survival in patients with epithelial ovarian cancer. Clin Cancer Res. 2005 Dec 15;11(24 Pt 1):8637–8643.PubMedGoogle Scholar
  46. 46.
    Crijns APG, Boezen HM, Schouten JP, et al. Prognostic factors in ovarian cancer: current evidence and future prospects. The ECCO 12 Educational Book Eur J Cancer. 2003;1(Suppl):127–145.Google Scholar
  47. 47.
    Baron AT, Boardman CH, Lafky JM, et al. Soluble epidermal growth factor receptor (sEGFR) and cancer antigen 125 (CA125) as screening and diagnostic tests for epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2005 Feb;14(2):306–318.PubMedGoogle Scholar
  48. 48.
    Lorimer IA. Mutant epidermal growth factor receptors as targets for cancer therapy. Curr Cancer Drug Targets. 2002 Jun;2(2):91–102.PubMedGoogle Scholar
  49. 49.
    Sonabend AM, Dana K, Lesniak MS. Targeting epidermal growth factor receptor variant III: a novel strategy for the therapy of malignant glioma. Expert Rev Anticancer Ther. 2007 Dec;7(12 Suppl):S45–S50.PubMedGoogle Scholar
  50. 50.
    Huang PH, Cavenee WK, Furnari FB, et al. Uncovering therapeutic targets for glioblastoma: a systems biology approach. Cell Cycle. 2007 Aug;6(22):2750–2754.PubMedGoogle Scholar
  51. 51.
    de Graeff P, Crijns AP, Ten Hoor KA, et al. The ErbB signalling pathway: protein expression and prognostic value in epithelial ovarian cancer. Br J Cancer. 2008 Jul 22;99(2):341–349.PubMedGoogle Scholar
  52. 52.
    Steffensen KD, Waldstrøm M, Olsen DA, et al. Mutant epidermal growth factor receptor in benign, borderline, and malignant ovarian tumors. Clin Cancer Res. 2008 Jun 1;14(11):3278–3282.PubMedGoogle Scholar
  53. 53.
    Ferguson KM. Structure-based view of epidermal growth factor receptor regulation. Annu Rev Biophys. 2008;37:353–373.PubMedGoogle Scholar
  54. 54.
    Kumar A, Petri ET, Halmos B, et al. Structure and clinical relevance of the epidermal growth factor receptor in human cancer. J Clin Oncol. 2008 Apr 1;26(10):1742–1751.PubMedGoogle Scholar
  55. 55.
    Tsakiridis T, Cutz JC, Singh G, et al. Association of phosphorylated epidermal growth factor receptor with survival in patients with locally advanced non-small cell lung cancer treated with radiotherapy. J Thorac Oncol. 2008 Jul;3(7):716–722.PubMedGoogle Scholar
  56. 56.
    Sonnweber B, Dlaska M, Skvortsov S, et al. High predictive value of epidermal growth factor receptor phosphorylation but not of EGFRvIII mutation in resected stage I non-small cell lung cancer (NSCLC). J Clin Pathol. 2006 Mar;59(3):255–259.PubMedGoogle Scholar
  57. 57.
    Kanematsu T, Yano S, Uehara H, et al. Phosphorylation, but not overexpression, of epidermal growth factor receptor is associated with poor prognosis of non-small cell lung cancer patients. Oncol Res. 2003;13(5):289–298.PubMedGoogle Scholar
  58. 58.
    Papouchado B, Erickson LA, Rohlinger AL, et al. Epidermal growth factor receptor and activated epidermal growth factor receptor expression in gastrointestinal carcinoids and pancreatic endocrine carcinomas. Mod Pathol. 2005 Oct;18(10):1329–1335.PubMedGoogle Scholar
  59. 59.
    Kong A, Leboucher P, Leek R, et al. Prognostic value of an activation state marker for epidermal growth factor receptor in tissue microarrays of head and neck cancer. Cancer Res. 2006;66(5):2834–2843.PubMedGoogle Scholar
  60. 60.
    Guo L, Abraham J, Flynn DC, Castranova V, Shi X, Qian Y. Individualized survival and treatment response predictions for breast cancers using phospho-EGFR, phospho-ER, phospho-HER2/neu, phospho-IGF-IR/In,phospho-MAPK, and phospho-p70S6K proteins. Int J Biol Markers. 2007 Jan-Mar;22(1):1–11.PubMedGoogle Scholar
  61. 61.
    Posadas EM, Liel MS, Kwitkowski V, et al. A phase II and pharmacodynamic study of gefitinib in patients with refractory or recurrent epithelial ovarian cancer. Cancer. 2007 Apr 1;109(7):1323–1330.PubMedGoogle Scholar
  62. 62.
    Cowden Dahl KD, Symowicz J, Ning Y, et al. Matrix metalloproteinase 9 is a mediator of epidermal growth factor-dependent e-cadherin loss in ovarian carcinoma cells. Cancer Res. 2008 Jun 15;68(12):4606–4013.PubMedGoogle Scholar
  63. 63.
    Siemens CH, Auersperg N. Serial propagation of human ovarian surface epithelium in tissue culture. J Cell Physiol. 1988 Mar;134(3):347–356.PubMedGoogle Scholar
  64. 64.
    McClellan M, Kievit P, Auersperg N, et al. Regulation of proliferation and apoptosis by epidermal growth factor and protein kinase C in human ovarian surface epithelial cells. Exp Cell Res. 1999 Feb 1;246(2):471–479.PubMedGoogle Scholar
  65. 65.
    Abdollahi A, Gruver BN, Patriotis C, et al. Identification of epidermal growth factor-responsive genes in normal rat ovarian surface epithelial cells. Biochem Biophys Res Commun. 2003 Jul 18;307(1):188–197.PubMedGoogle Scholar
  66. 66.
    Berchuck A, Olt GJ, Everitt L, et al. The role of peptide growth factors in epithelial ovarian cancer. Obstet Gynecol. 1990;75(2):255–262.PubMedGoogle Scholar
  67. 67.
    Crew AJ, Langdon SP, Miller EP, et al. Mitogenic effects of epidermal growth factor and transforming growth factor-alpha on EGF-receptor positive human ovarian carcinoma cell lines. Eur J Cancer. 1992;28(2–3):337–341.PubMedGoogle Scholar
  68. 68.
    Ferrandina G, Scambia G, Benedetti Panici P, et al. Effects of dexamethasone on the growth and epidermal growth factor receptor expression of the OVCA 433 ovarian cancer cells. Mol Cell Endocrinol. 1992 Feb;83(2–3):183–193.PubMedGoogle Scholar
  69. 69.
    Zhou L, Leung BS. Growth regulation of ovarian cancer cells by epidermal growth factor and transforming growth factors alpha and beta 1. Biochim Biophys Acta. 1992 Dec 10;1180(2):130–136.PubMedGoogle Scholar
  70. 70.
    Simpson BJ, Bartlett JM, Macleod KG, et al. Inhibition of transforming growth factor alpha (TGF-alpha)-mediated growth effects in ovarian cancer cell lines by a tyrosine kinase inhibitor ZM 252868. Br J Cancer. 1999 Mar;79(7–8):1098–1103.PubMedGoogle Scholar
  71. 71.
    Chen Z, Fadiel A, Feng Y, et al. Ovarian epithelial carcinoma tyrosine phosphorylation, cell proliferation, and ezrin translocation are stimulated by interleukin 1alpha and epidermal growth factor. Cancer. 2001 Dec 15;92(12):3068–3075.PubMedGoogle Scholar
  72. 72.
    Sewell JM, Macleod KG, Ritchie A, et al. Targeting the EGF receptor in ovarian cancer with the tyrosine kinase inhibitor ZD 1839 (“Iressa”). J Cancer. 2002 Feb 1;86(3):456–462.Google Scholar
  73. 73.
    Maihle NJ, Baron AT, Barrette BA, et al. EGF/ErbB receptor family in ovarian cancer. Cancer Treat Res. 2002;107:247–258.PubMedGoogle Scholar
  74. 74.
    Alper O, De Santis ML, Stromberg K, et al. Anti-sense suppression of epidermal growth factor receptor expression alters cellular proliferation, cell-adhesion and tumorigenicity in ovarian cancer cells. Int J Cancer. 2000;88(4):566–574.PubMedGoogle Scholar
  75. 75.
    Alper O, Bergmann-Leitner ES, Bennett TA, et al. Epidermal growth factor receptor signaling and the invasive phenotype of ovarian carcinoma cells. J Natl Cancer Inst. 2007;93:1375–1384.Google Scholar
  76. 76.
    Brader KR, Wolf JK, Chakrabarty S, et al. Epidermal growth factor receptor (EGFR) antisense transfection reduces the expression of EGFR and suppresses the malignant phenotype of a human ovarian cancer cell line. Oncol Rep. 1998;5:1269–1274.PubMedGoogle Scholar
  77. 77.
    Pack SD, Alper OM, Stromberg K, et al. Simultaneous suppression of epidermal growth factor receptor and c-erbB-2 reverses aneuploidy and malignant phenotype of a human ovarian carcinoma cell line. Cancer Res. 2004;64(3):789–794.PubMedGoogle Scholar
  78. 78.
    Kurachi H, Morishige K, Adachi H, et al. Implantation and growth of epidermal growth factor (EGF) receptor expressing human ovarian cancer xenografts in nude mice is dependent on EGF. Cancer. 1994 Dec 1;74(11):2984–2990.PubMedGoogle Scholar
  79. 79.
    Baguley BC, Marshall ES, Holdaway KM, et al. Inhibition of growth of primary human tumour cell cultures by a 4-anilinoquinazoline inhibitor of the epidermal growth factor receptor family of tyrosine kinases. Eur J Cancer. 1998 Jun;34(7):1086–1090.PubMedGoogle Scholar
  80. 80.
    Sirotnak FM. Studies with ZD1839 in preclinical models. Semin Oncol. 2003 Feb;30(1 Suppl 1):12–20.PubMedGoogle Scholar
  81. 81.
    Park SJ, Armstrong S, Kim Ch, et al. Lack of EGF receptor contributes to drug sensitivity of human germline cells. Br J Cancer. 2005;92:334–341.PubMedGoogle Scholar
  82. 82.
    Wosikowski K, Schuurhuis D, Kops GJ, et al. Altered gene expression in drug-resistant human breast cancer cells. Clin Cancer Res. 1997;3:2405–2414.PubMedGoogle Scholar
  83. 83.
    Dickstein BM, Wosikowski K, Bates SE. Increased resistance to cytotoxic agents in ZR75B human breast cancer cells transfected with epidermal growth factor receptor. Mol Cell Endocrinol. 1995;110:205–211.PubMedGoogle Scholar
  84. 84.
    Melisi D, Troiani T, Damiano V, et al. Therapeutic integration of signal transduction targeting agents and conventional anti-cancer treatments. Endocr Relat Cancer. 2004 Mar;11(1):51–68.PubMedGoogle Scholar
  85. 85.
    Wang F, Liu R, Lee SW, et al. Heparin-binding EGF-like growth factor is an early response gene to chemotherapy and contributes to chemotherapy resistance. Oncogene. 2007 Mar 29;26(14):2006–2016.PubMedGoogle Scholar
  86. 86.
    Peng XH, Karna P, Cao Z, et al. Cross-talk between epidermal growth factor receptor and hypoxia-inducible factor-1alpha signal pathways increases resistance to apoptosis by up-regulating surviving gene expression. J Biol Chem. 2006 Sep 8;281(36):25903–25914.Google Scholar
  87. 87.
    Milas L, Raju U, Liao Z, et al. Targeting molecular determinants of tumor chemo-radioresistance. Semin Oncol. 2005 Dec;32(6 Suppl 9):S78–S81.PubMedGoogle Scholar
  88. 88.
    Thariat J, Yildirim G, Mason KA, et al. Combination of radiotherapy with EGFR antagonists for head and neck carcinoma. Int J Clin Oncol. 2007 Apr;12(2):99–110.PubMedGoogle Scholar
  89. 89.
    Milano G, Spano JP, Leyland-Jones B. EGFR-targeting drugs in combination with cytotoxic agents: from bench to bedside, a contrasted reality. Br J Cancer. 2008 Jul 8;99(1):1–5.PubMedGoogle Scholar
  90. 90.
    Tortora G, Gelardi T, Ciardiello F, et al. The rationale for the combination of selective EGFR inhibitors with cytotoxic drugs and radiotherapy. Int J Biol Markers. 2007 Jan–Mar;22(1 Suppl 4):S47–S52.PubMedGoogle Scholar
  91. 91.
    Le Tourneau C, Siu LL. Molecular-targeted therapies in the treatment of squamous cell carcinomas of the head and neck. Curr Opin Oncol. 2008 May;20(3):256–263.PubMedGoogle Scholar
  92. 92.
    Chan JK, Pham H, You XJ, et al. Suppression of ovarian cancer cell tumorigenicity and evasion of Cisplatin resistance using a truncated epidermal growth factor receptor in a rat model. Cancer Res. 2005 Apr 15;65(8):3243–3248.PubMedGoogle Scholar
  93. 93.
    Ciardiello F, Caputo R, Bianco R, et al. Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin Cancer Res. 2000 May;6(5):2053–2063.PubMedGoogle Scholar
  94. 94.
    Coley, HM, Shotton CF, Ajose-Adeogun A, et al. Receptor tyrosine kinase (RTK) inhibition is effective in chemosensitising EGFR-expressing drug resistant human ovarian cancer cell lines when used in combination with cytotoxic agents. Biochem Pharmacol. 2006 Oct 16;72(8):941–948.PubMedGoogle Scholar
  95. 95.
    del Carmen MG, Rizvi I, Chang Y, et al. Synergism of epidermal growth factor receptor-targeted immunotherapy with photodynamic treatment of ovarian cancer in vivo. J Natl Cancer Inst. 2005 Oct 19;97(20):1516–1524.PubMedGoogle Scholar
  96. 96.
    Christen RD, Hom DK, Porter DC, et al. Epidermal growth factor regulates the in vitro sensitivity of human ovarian carcinoma cells to cisplatin. J Clin Invest. 1990 Nov;86(5):1632–1640.PubMedGoogle Scholar
  97. 97.
    Christen RD, Isonishi S, Jones JA, et al. Signaling and drug sensitivity. Cancer Metastasis Rev. 1994 Jun;13(2):175–189.PubMedGoogle Scholar
  98. 98.
    Kröning R, Jones JA, Hom DK, et al. Enhancement of drug sensitivity of human malignancies by epidermal growth factor. Br J Cancer. 1995 Sep;72(3):615–619.PubMedGoogle Scholar
  99. 99.
    Cao C, Lu S, Sowa A, Kivlin et al. Priming with EGFR tyrosine kinase inhibitor and EGF sensitizes ovarian cancer cells to respond to chemotherapeutical drugs. Cancer Lett. 2008 Aug 8;266(2):249–262.PubMedGoogle Scholar
  100. 100.
    Ciardiello F, Bianco R, Damiano V, et al. Antitumor activity of sequential treatment with topotecan and anti-epidermal growth factor receptor monoclonal antibody C225. Clin Cancer Res. 1999 Apr;5(4):909–916.PubMedGoogle Scholar
  101. 101.
    Mendelsohn J, Fan Z. Epidermal growth factor receptor family and chemosensitization. J Natl Cancer Inst. 1997 Mar 5;89(5):341–343.PubMedGoogle Scholar
  102. 102.
    Xu JM, Azzariti A, Severino M, et al. Characterization of sequence-dependent synergy between ZD1839 (“Iressa”) and oxaliplatin. Biochem Pharmacol. 2003 Aug 15;66(4):551–563.PubMedGoogle Scholar
  103. 103.
    Xu JM, Azzariti A, Colucci G, et al. The effect of gefitinib (Iressa, ZD1839) in combination with oxaliplatin is schedule-dependent in colon cancer cell lines. Cancer Chemother Pharmacol. 2003 Dec;52(6):442–448.PubMedGoogle Scholar
  104. 104.
    Azzariti A, Xu JM, Porcelli L, et al. The schedule-dependent enhanced cytotoxic activity of 7-ethyl-10-hydroxy-camptothecin (SN-38) in combination with Gefitinib (Iressa, ZD1839). Biochem Pharmacol. 2004 Jul 1;68(1):135–144.PubMedGoogle Scholar
  105. 105.
    Hay, ED. EMT concept and examples from the vertebrate embryo. In: Savagner P, ed. Rise and Fall of Epithelial Phenotype: Concepts of Epithelial-Mesenchymal Transition. Berlin: Springer; 2005:111–134.Google Scholar
  106. 106.
    Huber MA, Kraut N, Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol. 2005;17:548–558.PubMedGoogle Scholar
  107. 107.
    Van Marck VL, Bracke ME. Epithelial-mesenchymal transitions in human cancer. In: Savagner P, ed. Rise and Fall of Epithelial Phenotype: Concepts of Epithelial-Mesenchymal Transition. Berlin: Springer; 2005:111–134.Google Scholar
  108. 108.
    Guarino M, Rubino B, Ballabio G. The role of epithelial-mesenchymal transition in cancer pathology. Pathology. 2007;39:305–318.PubMedGoogle Scholar
  109. 109.
    Tse JC, Kalluri R. Mechanisms of metastasis: epithelial-to-mesenchymal transition and contribution of tumor microenvironment. J Cell Biochem. 2007;101(4):816–829.PubMedGoogle Scholar
  110. 110.
    Ahmed N, Maines-Bandiera S, Quinn MA, et al. Molecular pathways regulating EGF-induced epithelio-mesenchymal transition in human ovarian surface epithelium. Am J Physiol Cell Physiol. 2006;290(6):C1532–C1542.PubMedGoogle Scholar
  111. 111.
    Sabbah M, Emami S, Redeuilh G, et al. Molecular signature and therapeutic perspective of the epithelial-to-mesenchymal transitions in epithelial cancers. Dug Resist Updat. 2008;11(4–5):123–151.Google Scholar
  112. 112.
    Barr S, Thomson S, Buck E, et al. Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like ransitions. Clin Exp Metastasis. 2008;25(6):685–693.PubMedGoogle Scholar
  113. 113.
    Lo HW, Hsu SC, Xia W, et al. Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial-mesenchymal transition in cancer cells via up-regulation of TWIST gene expression. Cancer Res. 2007 Oct 1;67(19):9066–9076.PubMedGoogle Scholar
  114. 114.
    Lee MY, Chou CY, Tang MJ, et al. Epithelial-mesenchymal transition in cervical cancer: Correlation with tumor progression, epidermal growth factor receptor overexpression, and snail up-regulation. Clin Cancer Res. 2008 Aug 1;14(15):4743–4750.PubMedGoogle Scholar
  115. 115.
    Uttamsingh S, Bao X, Nguyen KT, et al. Synergistic effect between EGF and TGF-beta1 in inducing oncogenic properties of intestinal epithelial cells. Oncogene. 2008 Apr 17;27(18):2626–2634.PubMedGoogle Scholar
  116. 116.
    Arnoux V, Côme C, Hudson, LG et al. Cutaneous wound reepithelialization: A partial and reversible EMT. In: Savagner P, ed. Rise and Fall of Epithelial Phenotype: Concepts of Epithelial-Mesenchymal Transition. Berlin: Springer, 2005:111–134.Google Scholar
  117. 117.
    Ellerbroek SM, Hudson LG, Stack MS. Proteinase requirements of epidermal growth factor-induced ovarian cancer cell invasion. Int J Cancer. 1998 Oct 29;78(3):331–337.PubMedGoogle Scholar
  118. 118.
    Ning Y, Zeineldin R, Liu Y, et al. Down-regulation of integrin alpha2 surface expression by mutant epidermal growth factor receptor (EGFRvIII) induces aberrant cell spreading and focal adhesion formation. Cancer Res. 2005 Oct 15;65(20):9280–9286.PubMedGoogle Scholar
  119. 119.
    Ellerbroek SM, Halbleib JM, Benavidez M, et al. Phosphatidylinositol 3-kinase activity in epidermal growth factor-stimulated matrix metalloproteinase-9 production and cell surface association. Cancer Res. 2001 Mar 1;61(5):1855–1861.PubMedGoogle Scholar
  120. 120.
    Fujimura M, Hidaka T, Saito S. Selective inhibition of the epidermal growth factor receptor by ZD1839 decreases the growth and invasion of ovarian clear cell adenocarcinoma cells. Clin Cancer Res. 2002 Jul;8(7):2448–2454.PubMedGoogle Scholar
  121. 121.
    Sewell JM, Smyth JF, Langdon SP. Role of TGF alpha stimulation of the ERK, PI3 kinase and PLC gamma pathways in ovarian cancer growth and migration. Exp Cell Res. 2005 Mar 10;304(1):305–316.PubMedGoogle Scholar
  122. 122.
    Qiu L, Zhou C, Sun Y, Di W, et al. Crosstalk between EGFR and TrkB enhances ovarian cancer cell migration and proliferation. Int J Oncol. 2006 Oct;29(4):1003–1011.PubMedGoogle Scholar
  123. 123.
    Henic E, Sixt M, Hansson S, et al. EGF-stimulated migration in ovarian cancer cells is associated with decreased internalization, increased surface expression, and increased shedding of the urokinase plasminogen activator receptor. Gynecol Oncol. 2006 Apr;101(1):28–39.PubMedGoogle Scholar
  124. 124.
    Cowden Dahl KD, Zeineldin R, Hudson LG. PEA3 is necessary for optimal epidermal growth factor receptor-stimulated matrix metalloproteinase expression and invasion of ovarian tumor cells. Mol Cancer Res. 2007 May;5(5):413–421.PubMedGoogle Scholar
  125. 125.
    Zeineldin R, Rosenberg M, Ortega D, et al. Mesenchymal transformation in epithelial ovarian tumor cells expressing epidermal growth factor receptor variant III. Mol Carcinog. 2006 Nov;45(11):851–860.PubMedGoogle Scholar
  126. 126.
    Rosanò L, Di Castro V, Spinella F, et al. Combined targeting of endothelin A receptor and epidermal growth factor receptor in ovarian cancer shows enhanced antitumor activity. Cancer Res. 2007 Jul 1;67(13):6351–6359.PubMedGoogle Scholar
  127. 127.
    Rosso O, Piazza T, Bongarzone I, et al. The ALCAM shedding by the metalloprotease ADAM17/TACE is involved in motility of ovarian carcinoma cells. Mol Cancer Res. 2007 Dec;5(12):1246–1253.PubMedGoogle Scholar
  128. 128.
    Zhou HY, Pon YL, Wong AS. Synergistic effects of epidermal growth factor and hepatocyte growth factor on human ovarian cancer cell invasion and migration: role of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase. Endocrinology. 2007 Nov;148(11):5195–5208.PubMedGoogle Scholar
  129. 129.
    Matsuzaki H, Kobayashi H, Yagyu T, et al. Reduced syndecan-1 expression stimulates heparin-binding growth factor-mediated invasion in ovarian cancer cells in a urokinase independent mechanism. Oncol Rep. 2005 Aug;14(2):449–457.PubMedGoogle Scholar
  130. 130.
    Ueda M, Ueki M, Terai Y, et al. Biological implications of growth factors on the mechanism of invasion in gynecological tumor cells. Gynecol Obstet Invest. 1999;48(3):221–228.PubMedGoogle Scholar
  131. 131.
    Galway AB, Oikawa M, Ny T, et al. Epidermal growth factor stimulates tissue plasminogen activator activity and messenger ribonucleic acid levels in cultured rat granulosa cells: mediation by pathways independent of protein kinases-A and -C. Endocrinology. 1989 Jul;125(1):126–135.PubMedGoogle Scholar
  132. 132.
    Fodde R, Brabletz T. Wnt/beta-catenin signaling in cancer stemness and malignant behavior. Curr Opin Cell Biol. 2007;19:150–158.PubMedGoogle Scholar
  133. 133.
    Hudson LG, Zeineldin R, Stack MS. Phenotypic plasticity of neoplastic ovarian epithelium: unique cadherin profiles in tumor progression. Clin Exp Metastasis. 2008;25(6):643–655.PubMedGoogle Scholar
  134. 134.
    diZerega GS and Rodgers KE. Peritoneal Exudate. The Peritoneum, Berlin: Springer Verlag; 1992:26–56.Google Scholar
  135. 135.
    Shen-Gunther J, Mannel RS. Ascites as a predictor of ovarian malignancy. Gynecol Oncol. 2002 Oct;87(1):77–83.PubMedGoogle Scholar
  136. 136.
    Faça VM, Ventura AP, Fitzgibbon MP, et al. Proteomic analysis of ovarian cancer cells reveals dynamic processes of protein secretion and shedding of extra-cellular domains. PLoS ONE. 2008 Jun 18;3(6):e2425.PubMedGoogle Scholar
  137. 137.
    Miyamoto S, Yagi H, Yotsumoto F, et al. New approach to cancer therapy: heparin binding-epidermal growth factor-like growth factor as a novel targeting molecule. Anticancer Res. 2007 Nov–Dec;27(6A):3713–3721.PubMedGoogle Scholar
  138. 138.
    Miyamoto S, Yagi H, Yotsumoto F, et al. Heparin-binding epidermal growth factor-like growth factor as a new target molecule for cancer therapy. Adv Exp Med Biol. 2008;622:281–295.PubMedGoogle Scholar
  139. 139.
    Braun AH, Coffey RJ. Lysophosphatidic acid, a disintegrin and metalloprotease-17 and heparin-binding epidermal growth factor-like growth factor in ovarian cancer: the first word, not the last. Clin Cancer Res. 2005 Jul 1;11(13):4639–4643.PubMedGoogle Scholar
  140. 140.
    Prenzel N, Zwick E, Daub H, et al. EGF receptor transactivation by G-protein-coupled receptors requires etalloproteinase cleavage of proHB-EGF. Nature. 1999 Dec 23–30;402(6764):884–888.PubMedGoogle Scholar
  141. 141.
    Hsieh M, Conti M. G-protein-coupled receptor signaling and the EGF network in endocrine systems. Trends Endocrinol Metab. 2005 Sep;16(7):320–326.PubMedGoogle Scholar
  142. 142.
    Fischer OM, Hart S, Ullrich A. Dissecting the epidermal growth factor receptor signal transactivation pathway. Methods Mol Biol. 2006;327:85–97.PubMedGoogle Scholar
  143. 143.
    Bhola NE, Grandis JR. Crosstalk between G-protein-coupled receptors and epidermal growth factor receptor in cancer. Front Biosci. 2008 Jan 1;13:1857–1865.PubMedGoogle Scholar
  144. 144.
    Herrmann E, Bögemann M, Bierer S, et al. The endothelin axis in urologic tumors: mechanisms of tumor biology and therapeutic implications. Expert Rev Anticancer Ther. 2006 Jan;6(1):73–81.PubMedGoogle Scholar
  145. 145.
    Lalich M, McNeel DG, Wilding G, et al. Endothelin receptor antagonists in cancer therapy. Cancer Invest. 2007 Dec;25(8):785–794.PubMedGoogle Scholar
  146. 146.
    Bagnato A, Rosanò L. The endothelin axis in cancer. Int J Biochem Cell Biol. 2008;40(8):1443–1451.PubMedGoogle Scholar
  147. 147.
    Meidan R, Levy N. The ovarian endothelin network: an evolving story. Trends Endocrinol Metab. 2007 Dec;18(10):379–385.PubMedGoogle Scholar
  148. 148.
    Bagnato A, Salani D, Di Castro V, et al. Expression of endothelin-1 and endothelin A receptor in ovarian carcinoma: evidence for an autocrine role in tumor growth. Cancer Res. 1999;59:1–8.Google Scholar
  149. 149.
    Salani D, Di Castro V, Nicotra MR, et al. Role of endothelin-1 in neovascularization of ovarian carcinoma. Am J Pathol. 2000;157:1537–1547.PubMedGoogle Scholar
  150. 150.
    Bagnato A, Tecce R, Di Castro V, et al. Activation of mitogenic signaling by endothelin-1 in ovarian carcinoma cells. Cancer Res. 1997;57:1306–1311.PubMedGoogle Scholar
  151. 151.
    Rosanò L, Varmi M, Salani D, et al. Endothelin-1 induces tumor proteinase activation and invasiveness of ovarian carcinoma cells. Cancer Res. 2001 Nov 15;61(22):8340–8346.PubMedGoogle Scholar
  152. 152.
    Rosanò L, Spinella F, Di Castro V, et al. Endothelin-1 is required during epithelial to mesenchymal transition in ovarian cancer progression. Exp Biol Med (Maywood). 2006 Jun;231(6):1128–1131.Google Scholar
  153. 153.
    Rosanò L, Di Castro V, Spinella F, et al. ZD4054, a potent endothelin receptor A antagonist, inhibits ovarian carcinoma cell proliferation. Exp Biol Med (Maywood). 2006 Jun;231(6):1132–1135.Google Scholar
  154. 154.
    Spinella F, Rosanò L, Elia G, et al. Endothelin-1 stimulates cyclooxygenase-2 expression in ovarian cancer cells through multiple signaling pathways: evidence for involvement of transactivation of the epidermal growth factor receptor. J Cardiovasc Pharmacol. 2004 Nov;44(Suppl 1):S140–S143.PubMedGoogle Scholar
  155. 155.
    Vacca F, Bagnato A, Catt KJ, et al. Transactivation of the epidermal growth factor receptor in endothelin-1-induced mitogenic signaling in human ovarian carcinoma cells. Cancer Res. 2000 Sep 15;60(18):5310–5317.PubMedGoogle Scholar
  156. 156.
    Fang X, Gaudette D, Furui T, et al. Lysophospholipid growth factors in the initiation, progression, metastases, and management of ovarian cancer. Ann NY Acad Sci. 2000 Apr;905:188–208.PubMedGoogle Scholar
  157. 157.
    Pustilnik TB, Estrella V, Wiener JR, et al. Lysophosphatidic acid induces urokinase secretion by ovarian cancer cells. Clin Cancer Res. 1999;5(11):3704–3710.PubMedGoogle Scholar
  158. 158.
    Fishman DA, Liu Y, Ellerbroek SM, et al. Lysophosphatidic acid promotes matrix metalloproteinase processing and MMP-dependent invasion in ovarian carcinoma cells. Cancer Res. 2001;61:3194–3199.PubMedGoogle Scholar
  159. 159.
    Symowicz J, Adley BP, Woo MMM, et al. Cyclooxygenase-2 functions as a downstream mediator of lysophosphatidic acid to promote aggressive behavior in ovarian carcinoma cells. Cancer Res. 2007;67(5):2030–2039.PubMedGoogle Scholar
  160. 160.
    Bian D, Su S, Mahanivong C, et al. Lysophosphatidic acid stimulates ovarian cancer cell migration via a ras-MEK kinase 1 pathway. Cancer Res. 2004;12:4209–4217.Google Scholar
  161. 161.
    Laffargue M, Raynal P, Yart A, et al. An 3-kinase by lysophosphatidic acid. J Biol Chem 1999; 274(46):32835–32841.PubMedGoogle Scholar
  162. 162.
    Kim SN, Park JG, Lee EB, et al. Characterization of epidermal growth factor receptor function in lysophosphatidic acid signaling in PC12 cells. J Cell Biochem. 2000;76(3):386–393.PubMedGoogle Scholar
  163. 163.
    Ghosh S, Wu Y, Stack MS. Ovarian cancer-associated proteinases. In Stack MS, Fishman DA, editors. Cancer treatment and research: Ovarian cancer. Boston: Kluwer Academic Press; 2002:331–352.Google Scholar
  164. 164.
    Symowicz J, Adley BP, Gleason KJ, et al. Engagement of collagen-binding integrins promotes matrix metalloproteinase-9-dependent E-cadherin ectodomain shedding in ovarian carcinoma cells. Cancer Res. 2007 Mar 1;67(5):2030–2039.PubMedGoogle Scholar
  165. 165.
    Do TV, Symowicz JC, Berman DM, et al. Lysophosphatidic acid down-regulates stress fibers and up-regulates pro-matrix metalloproteinase-2 activation in ovarian cancer cells. Mol Cancer Res. 2007 Feb;5(2):121–131.PubMedGoogle Scholar
  166. 166.
    Fisher KE, Pop A, Koh W, et al. Tumor cell invasion of collagen matrices requires coordinate lipid agonist-induced G-protein and membrane-type matrix metalloproteinase-1-dependent signaling. Mol Cancer. 2006 Dec 8;5:69.PubMedGoogle Scholar
  167. 167.
    Wang FQ, Smicun Y, Calluzzo N, et al. Inhibition of matrilysin expression by antisense or RNA interference decreases lysophosphatidic acid-induced epithelial ovarian cancer invasion. Mol Cancer Res. 2006 Nov;4(11):831–841.PubMedGoogle Scholar
  168. 168.
    So J, Navari J, Wang FQ, et al. Lysophosphatidic acid enhances epithelial ovarian carcinoma invasion through the increased expression of interleukin-8. Gynecol Oncol. 2004 Nov;95(2):314–322.PubMedGoogle Scholar
  169. 169.
    Huang LW, Garrett AP, Bell DA, et al. Differential expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 protein and mRNA in epithelial ovarian tumors. Gynecol Oncol. 2000;77:369–376.PubMedGoogle Scholar
  170. 170.
    Davidson B, Goldberg I, Gotlieb WH, et al. High levels of MMP2, MMP9, MT1-MMP and TIMP-2 mRNA correlate with poor survival in ovarian carcinoma. Clin Exp Metastasis 1999;17:799–808.PubMedGoogle Scholar
  171. 171.
    Naylor MS, Stamp GW, Davies BD, et al. Expression and activity of MMPs and their regulators in ovarian cancer. Int J Cancer. 1994;58:50–56.PubMedGoogle Scholar
  172. 172.
    Fishman DA, Bafetti LM, Banionis S, et al. Production of extracellular matrix-degrading proteinases by primary cultures of human epithelial ovarian carcinoma cells. Cancer. 1997;80:1457–1463.PubMedGoogle Scholar
  173. 173.
    Young TN, Rodriguez GC, Rindhart AR, et al. Characterization of gelatinases linked to extracellular matrix invasion in ovarian adenocarcinoma: purification of matrix metalloproteinase 2. Gynecol Oncol. 1996;62:89–99.PubMedGoogle Scholar
  174. 174.
    Fishman, DA, Bafetti, LM, Stack MS. Membrane-type matrix metalloproteinase expression and matrix metalloproteinase-2 activation in primary human ovarian epithelial carcinoma cells. Invasion Metastasis. 1996;16:150–159.PubMedGoogle Scholar
  175. 175.
    DeClerck YA. Interactions between tumour cells and stromal cells and proteolytic modification of the extracellular matrix by metalloproteinases in cancer. Eur J Cancer. 2000;36:1258–1268.PubMedGoogle Scholar
  176. 176.
    De Wever O, Derycke L, Hendrix A, et al. Soluble cadherins as cancer biomarkers. Clin Exp Metastasis. 2007;24(8):685–697.PubMedGoogle Scholar
  177. 177.
    Veatch AL, Carson LF, Ramakrishnan S. Differential expression of the cell-cell adhesion molecule E cadherin in ascites and solid human ovarian tumor cells. Int J Can. 1994;58:393–399.Google Scholar
  178. 178.
    Darai E, Bringuier AF, Walker-Combrouze F, et al. Soluble adhesion molecules in serum and cyst fluid from patients with cystic tumors of the ovary. Human Repord. 1997;13:2831–2835.Google Scholar
  179. 179.
    Sundfeldt K, Ivarsson K, Rask K, et al. Higher levels of soluble E-cadherin in cyst fluid from malignant ovarian tumors than in benign cysts. Anticancer Res. 2001;21:65–70.PubMedGoogle Scholar
  180. 180.
    Lu Z, Ghosh S, Wang Z, Hunter T. Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of beta-catenin, and enhanced tumor cell invasion. Cancer Cell. 2003;4(6):499–515.PubMedGoogle Scholar
  181. 181.
    Tsang WP, Kong SK, Kwok TT. Epidermal growth factor induction of resistance to topoisomerase II toxins in human squamous carcinoma A431 cells. Oncol Rep. 2006;16(4):789–793.PubMedGoogle Scholar
  182. 182.
    Sharif A, Legendre P, Prévot V, et al. Transforming growth factor alpha promotes sequential conversion of mature astrocytes into neural progenitors and stem cells. Oncogene. 2007 Apr 26;26(19):2695–2706.PubMedGoogle Scholar
  183. 183.
    Nagane M, Levitzki A, Gazit A, et al. Drug resistance of human glioblastoma cells conferred by a tumor-specific mutant epidermal growth factor receptor through modulation of Bcl-XL and caspase-3-like proteases. Proc Natl Acad Sci USA. 1998 May 12;95(10):5724–5729.PubMedGoogle Scholar
  184. 184.
    Weppler SA, Li Y, Dubois L, et al. Expression of EGFR variant vIII promotes both radiation resistance and hypoxia tolerance. Radiother Oncol. 2007 Jun;83(3):333–339.PubMedGoogle Scholar
  185. 185.
    Luwor RB, Zhu HJ, Walker F, et al. The tumor-specific de2-7 epidermal growth factor receptor (EGFR) promotes cells survival and heterodimerizes with the wild-type EGFR. Oncogene. 2004 Aug 12; 23(36):6095–6104.PubMedGoogle Scholar
  186. 186.
    Pedersen MW, Pedersen N, Damstrup L, et al. Analysis of the epidermal growth factor receptor specific transcriptome: effect of receptor expression level and an activating mutation. J Cell Biochem. 2005 Oct 1;96(2):412–427.PubMedGoogle Scholar
  187. 187.
    Pedersen MW, Tkach V, Pedersen N, Berezin V, Poulsen HS. Expression of a naturally occurring constitutively active variant of the epidermal growth factor receptor in mouse fibroblasts increases motility. Int J Cancer. 2004 Feb 20;108(5):643–653.PubMedGoogle Scholar
  188. 188.
    Lal A, Glazer CA, Martinson HM, et al. Mutant epidermal growth factor receptor up-regulates molecular effectors of tumor invasion. Cancer Res. 2002 Jun 15; 62(12):3335–3339.PubMedGoogle Scholar
  189. 189.
    Damstrup L, Wandahl Pedersen M, Bastholm L, Elling F, Skovgaard Poulsen H. Epidermal growth factor receptor mutation type III transfected into a small cell lung cancer cell line is predominantly localized at the cell surface and enhances the malignant phenotype. Int J Cancer. 2002 Jan 1;97(1):7–14.PubMedGoogle Scholar
  190. 190.
    Ning Y, Buranda T, Hudson LG. Activated epidermal growth factor receptor induces integrin alpha2 internalization via caveolae/raft-dependent endocytic pathway. J Biol Chem. 2007 Mar 2;282(9):6380–6387.PubMedGoogle Scholar
  191. 191.
    Radisky DC, Levy DD, Littlepage LE, et al. Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature. 2005 Jul 7;436(7047):123–127.PubMedGoogle Scholar
  192. 192.
    Sternlicht MD, Bissell MJ, Werb Z. The matrix metalloproteinase stromelysin-1 acts as a natural mammary tumor promoter. Oncogene. 2000 Feb 21;19(8):1102–1113.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Laurie G. Hudson
    • 1
    Email author
  • Reema Zeineldin
    • 1
  • Melina Silberberg
    • 1
  • M. Sharon Stack
    • 2
  1. 1.Department of Pharmaceutical Sciences, College of PharmacyUniversity of New MexicoAlbuquerqueUSA
  2. 2.Departments of Pathology & Anatomical Sciences; Medical Pharmacology & PhysiologyUniversity of Missouri School of MedicineColumbiaUSA

Personalised recommendations