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Proliferation of Rhesus Ovarian Surface Epithelial Cells in Culture: Lack of Mitogenic Response to Steroid or Gonadotropic Hormones

Departments of Cell and Developmental Biology (J.W.W., K.D.R.), Surgical Oncology (S.T.-F.), and Physiology and Pharmacology (R.L.S.), Oregon Health Sciences University, Portland, Oregon 97201; Division of Reproductive Sciences (R.L.S.), Oregon Regional Primate Research Center, Beaverton, Oregon 97006; and Molecular Biosciences (K.D.R.), Pacific Northwest National Laboratory, Richland, Washington 99352

Address all correspondence and requests for reprints to: Karin Rodland, Pacific Northwest National Laboratory, Department of Cell and Developmental Biology, 902 Battelle Boulevard, P.O. Box 999, Richland, Washington 99353. E-mail: . Karin.Rodland{at}pnl.gov

Ovarian cancer is the most lethal gynecological cancer, and approximately 90% of ovarian cancers derive from the ovarian surface epithelium (OSE), yet the biology of the OSE is poorly understood. Factors associated with increased risk of nonhereditary ovarian cancer include the formation of inclusion cysts, effects of reproductive hormones and the number of ovulations experienced in a woman’s lifetime. Distinguishing between these factors is difficult in vivo, but cultured OSE cells are viable tools for some avenues of research. Here we establish rhesus macaque OSE cultures and demonstrate that these cells express cytokeratin, vimentin, N-cadherin, ER-, and PR but are negative for E-cadherin. We show that these cells activate MAPK and proliferate in response to extracellular calcium, as do human and rat OSE. In contrast, the gonadotropic hormones FSH (4–400 IU/liter), LH (8.5–850 IU/liter), and human CG (10–1000 IU/liter) fail to stimulate proliferation. We find that concentrations of progesterone and estrogen normally present in follicles just before ovulation (1000 ng/ml) significantly decrease the number of mitotically active rhesus macaque OSE cells as determined by PCNA labeling, total cell count, and ³H-thymidine uptake, whereas lower steroid concentrations have no effect.

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