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Clin Cancer Res ; 4(9): 2245-51, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9748145

ABSTRACT

Here, we sought to obtain evidence that the progesterone receptor (PR) may be functional in ovarian cancer and regulated by estrogen. Megestrol acetate inhibited growth of the PR-positive PE04 ovarian carcinoma xenograft but not the PR-negative HOX 60 xenograft. PR concentration was higher in early-stage (I/II) tumors than in advanced-stage (III/IV) tumors (P = 0.007) and in tumors of endometrioid histology compared to other carcinoma subtypes (P = 0.009). Patients with a tumor PR concentration of >40 fmol/mg protein had significantly improved survival over those patients whose tumors contained <40 fmol/mg (P = 0.0007; log-rank). Evidence of PR regulation by estrogen was obtained by endocrine manipulation of the PE04 xenograft. PR content of PE04 xenografts fell from 145 to 7 fmol/mg protein in ovariectomized mice and was 2 fmol/mg in male mice. Administration of 17-beta-estradiol increased PR content to 745 fmol/mg. In primary ovarian carcinomas, PR was significantly associated with ER concentrations (P < 0.0001), suggesting regulation of PR levels by estrogen. This association was present for tumors of endometrioid histology (P < 0.0001) but not for those with serous histology (P = 0.31). These data point to the regulation of PR levels by estrogen in ovarian cancer and to a mediatory role for PR in the inhibition of growth induced by progestin.


Subject(s)
Estrogens/physiology , Ovarian Neoplasms/ultrastructure , Receptors, Progesterone/physiology , Animals , Cell Division/drug effects , Estradiol/pharmacology , Female , Humans , Immunoenzyme Techniques , Male , Megestrol Acetate/pharmacology , Mice , Mice, Nude , Neoplasm Transplantation , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Receptors, Estrogen/physiology , Receptors, Progesterone/drug effects , Receptors, Progesterone/metabolism , Transplantation, Heterologous , Tumor Cells, Cultured
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