Functionality of the progesterone receptor in ovarian cancer and its regulation by estrogen

Clin Cancer Res. 1998 Sep;4(9):2245-51.


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.

MeSH terms

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


  • Estrogens
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Estradiol
  • Megestrol Acetate