Growth factors interact with estradiol and gonadotropins in the regulation of ovarian cancer cell growth and growth factor receptors.
The factors controlling cell growth in epithelial ovarian cancer (OV Ca) remain poorly defined. Epidemiological evidence suggests that gonadotropins and estrogens may be important in the development of OV Ca. We have established permanent cultures of OV Ca cells from a mesenteric metastasis of an ovarian papillary adenocarcinoma. The growth of these cells was increased 20-60% (p < 0.01) by picomolar concentrations of 17 beta-E2 (but not by 17 alpha-E2) and 0.1 to 1 microgram/mL of hCG (but not hFSH). Both EGF and IGF-1 increased cell growth, and a maximal effect of 3- to 5-fold increase in cell number was observed. Under conditions in which the growth responses to EGF and IGF-1 were submaximal, E2 (0.1 to 100 nM) produced a concentration related increase in the growth response to IGF-1 and EGF. Ten nM E2 increased the responses to EGF and IGF-1 more than 2-fold. In combination, E2/hCG enhanced the growth response to EGF but not to IGF-1. Estradiol increased the Ka of the EGF receptor approximately 2-fold (p < 0.01) and increased the number of receptors/cell for IGF-1 approximately 50% (p < 0.01). While hCG had no effect on EGF receptor binding parameters, it increased the Ka of the IGF-1 receptor and enhanced the effect of E2 on IGF-1 receptor number. These studies suggest that E2 and hCG may regulate cell growth responses of OV Ca cells to IGF-1 and EGF. These changes may be exerted at least partly through modulation of properties of receptors for the two growth factors.
Department of Obstetrics/Gynecology, Graduate School of Medicine, University of Tennessee Medical Center, Knoxville 37920.
J
J
Wimalasena
D
D
Meehan
R
R
Dostal
J S
JS
Foster
M
M
Cameron
M
M
Smith
D000231:Adenocarcinoma, Papillary / Q000473:pathology*; D000368:Aged; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
D006063:Chorionic Gonadotropin; D004958:Estradiol; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1