Abstract
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.
Keywords
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Article info
Publication history
Received:
March 25,
2004
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© 2004 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
