Biologjia Online

The expression of progesterone receptor (PR) is normally estrogen-dependent and progesterone is only active in target cells following estrogen exposure. This study has revealed that the effect of estrogen was markedly disrupted by estrogen-independent expression of PR. Transfection of PR in the estrogen receptor (ER)-positive MCF-7 cells abolished estradiol-17ß’s growth stimulatory effect that was observed in the parental cells and the vector-transfected controls in a ligand-independent manner. The antiestrogenic effect was also observed at the level of gene transcription. Estradiol-17ß (E2)-induced gene expression of pS2 and GREB1 was impaired by 50 – 75% after 24 h - 72 h of E2 treatment in PR-transfected cells. Promoter interference assay revealed that PR transfection drastically inhibited E2-mediated ER binding to estrogen response elements (ERE). The antiestrogenic effects of transfected PR are associated with enhanced metabolism of E2. HPLC analysis of [3H]-E2 in the media samples indicated that the percentage of [3H]-E2 metabolized by PR-transfected cells in 6 h is similar to that by vector-transfected control cells in 24 h (77% and 80% respectively). The increased metabolism of E2 may, in turn, be caused by increased cellular uptake of E2, as demonstrated by whole cell binding of [3H]-E2. The findings open up a new window for a hitherto unknown functional relationship between the PR and ER. The antiestrogenic effect of transfected PR also provides a potential therapeutic strategy for estrogen-dependent breast cancer.