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The Activity of Medroxyprogesterone Acetate, an Androgenic Ligand, in Ovarian Cancer Cell Invasion

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, New York University, New York

Marek Kudla, MD

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, New York University, New York

Orlando Gil, PhD

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, New York University, New York

David Fishman, MD

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, New York University, New York, David.fishman{at}nyumc.org

Objectives: An epithelial ovarian cancer cell line constitutively expressing the androgen receptor was created to evaluate the mechanism and effects of androgen receptor activation on epithelial ovarian cancer cell invasion. Methods: Immunocytochemistry and Western blot analyses confirmed androgen receptor expression. Boyden chamber invasion assays were performed using cells treated with the androgen receptor ligands medroxyprogesterone acetate or dihydrotestosterone. The matrix metalloproteinases associated with invasion were investigated using zymographic assays. Results: Androgen receptor—mediated invasion is ligand dependent. While both medroxyprogesterone acetate and dihydrotestosterone signal through androgen receptor, medroxyprogesterone acetate is more effective at stimulating invasion of epithelial ovarian cancer cells. Unlike the wild-type epithelial ovarian cancer cells, this increase in invasion in androgen receptor+ epithelial ovarian cancer cells does not seem to be dependent on matrix metalloproteinase 2 or 9 activation. Conclusion: Although classified as a progestin, medroxyprogesterone acetate has significant androgenic activity unique from the pure androgen dihydrotestosterone. Our studies suggest that pharmacologic doses of medroxyprogesterone acetate may actually increase the invasive potential of epithelial ovarian cancer cells.

Key Words: Androgen receptor • ovarian cancer • synthetic progestins.

Reproductive Sciences, Vol. 15, No. 8, 846-852 (2008)
DOI: 10.1177/1933719108323446


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