Estrogen and Anti-Estrogen Effects on the Growth of Human Epithelial Ovarian Cancer In Vitro

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Abstract
An epithlial ovarian cancer cell line, PEO4, has been shown to contain high levels of cytosolic estrogen receptor-like binding. Analysis of PEO4 cytosol on low-salt sucrose density gradients demonstrated 7-9S binding of [3H]17.beta.-estradiol, with specificity consistent with that of an estrogen receptor. When compared with the proliferation of cells grown in monolayer without steroids, a 50% increase in growth rate of the cell line was observed by treatment with 17.beta.-estradiol(E2). Growth stimulation was dose-dependent and maximal at 10-10 M. The E2 effect on substrate-independent growth was more striking; 3 .times. 10-9 M produced a 30-fold increase in cloning efficiency. Treatment with 4-hydroxytamoxifen resulted in a dose-dependent inhibition (maximal at 3 7x 10-9 M) of cell growth, which was reversible by E2. Although treatment with estrogen in systems containing functional estrogen receptor commonly results in progesterone receptor synthesis, E2 induction of progesterone receptor could not be demonstrated in this cell line. The endocrine characteristics of PEO4 contrast with those of another ovarian cancer cell line, NIH:OVCAR-3, in which E2 induces progesterone receptor but does not stimulate cell proliferation. This is the first report of an ovarian cancer cell line in which the clinically important end-effect of estrogen, cell growth, has been observed. Furthermore, retention of a mitogenic response to estrogen in the apparent absence of progesteron receptor induction has not been described previously in model systems. Further study of PEO4 may help elucidate the significance of steroids in the biology of common epithelial tumors of the ovary and may help optimize hormonal therapy of ovarian cancer.