Research Article| Volume 94, ISSUE 3, P705-712, September 2004

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Estrogen receptor-positive human epithelial ovarian carcinoma cells respond to the antitumor drug suramin with increased proliferation: possible insight into ER and epidermal growth factor signaling interactions in ovarian cancer


      Objectives. Development of targeted therapeutics for ovarian cancer requires a basic understanding of ovarian epithelial carcinoma cell biology. The role of estrogen and epidermal growth factor (EGF) in control of cell growth was investigated in a panel of ovarian carcinoma lines.
      Methods. EGF receptor (EGFR) was detected by flow cytometry and estrogen receptor (ER) by Northern blot. Western blotting and [3H]thymidine incorporation were used to determine receptor activation and the effects of ligand exposure and growth factor antagonists, including the antineoplastic agent, suramin, on cell growth.
      Results. Only one cell line, OV266, expressed ER and responded to β-estradiol with increases in DNA synthesis and cell proliferation that could be blocked by the pure antiestrogen ICI 182,780. All cell lines possessed functional EGFR as measured by flow cytometry and phosphorylation of the receptor and mitogen-activated protein kinase after EGF treatment, but only two cell lines (OV177 and OV266) proliferated in response to exogenous EGF. Suramin had limited effectiveness in inhibiting growth in four of five cell lines and had a striking dose-dependent stimulatory effect on OV266 cell growth. The proliferative response to suramin could be inhibited with EGFR antagonists.
      Conclusion. Cultured epithelial ovarian carcinoma cell lines express EGFR (5/5) and can express ER (1/5). Differential growth responses to EGF were observed despite uniform receptor and MAPK activation. Unexpectedly, the antineoplastic agent suramin increased growth of ER positive ovarian carcinoma cells in an EGFR-dependent manner. These studies provide insight into the complex interactions of these systems in control of ovarian cancer cell growth.


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