The presence of a membrane-bound progesterone receptor sensitizes the estradiol-induced effect on the proliferation of human breast cancer cells

Objective: Breast cancer risk is still an important topic regarding hormone therapy as well as oral contraception. Evidence that progestogens may play a crucial role is accumulating. Progesterone receptor membrane component 1 (PGRMC1) expressed in breast cancer may be important in tumorigenesis and thus may increase breast cancer risk. The aim of this project was to investigate the influence of different estradiol (E-2) concentrations and the addition of two progestogens on MCF-7 breast cancer cells overexpressing PGRMC1. Methods: MCF-7 cells were stably transfected with PGRMC1 expression plasmid (MCF-7/PGRMC1-3HA [WT-12]). To test the effects of E-2 and progestogens on cell proliferation, MCF-7 and WT-12 cells were stimulated with different concentrations of E-2 (10(-10) and 10(-12) M) alone and in combination with progesterone and medroxyprogesterone acetate (each 10(-6) M). Results: E-2 elicited a concentration-dependent proliferative effect on both cell lines, which was much more pronounced in WT-12 cells (50% vs 200%). This effect could be completely abrogated by the addition of the E-2 antagonist fulvestrant. Addition of progesterone had no influence on the E-2-induced effect, whereas medroxyprogesterone acetate enhanced the E-2-induced effect at a low E-2 concentration, which was, again, more pronounced in the WT-12 cells. The figures were between 20% and 40% in MCF-7 and between 60% and 250% in WT-12 cells. Conclusions: Overexpression of PGRMC1 sensitizes the proliferative response of the MCF-7 breast cancer cell line to estradiol. The effect of progestogens on breast cancer tumorigenesis may depend on the specific progestogen used for hormone therapy or oral contraception.