RU486, A Progestin and Glucocorticoid Antagonist, Inhibits the Growth of Breast Cancer Cells via the Progesterone Receptor*

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Abstract
The progestin and glucocorticoid antagonist RU486 was tested on the growth of severalcell lines in culture. RU486 inhibited the growth of two progesterone receptor (RP) positive humanbreast cancer cell lines (MCF7 and T47D). The antiproliferative effect was dose dependent and its magnitude correlated with the RP content of the tested cells (T47D > estradiol-primed MCF7 > withdrawn MCF7). Cell growth inhibition was not prevented by the addition of dexamethasone,dihydrotestosterone, or estradiol, but the cells were rescued by low concentrations of the progestin R5020. RU486 had no effect on the growth of two RP negative human breast cancer cell lines andarat fibroblast cell line. Moreover, RU486 had no progestin agonist activity in T47D cells when evaluated by measuring the =S-labeling of two progestin-regulated proteins with mol wts of 48,000 and250,000, but it totally prevented the induction of these two proteins by R5020. In conclusion, RU486 selectively inhibited the growth of human breast cancer cell lines with unoccupied RP sites andits effect was correlated with the RP concentration of these cells. We propose that RU486 is aRP-targeted drug of potential utility in breast cancer treatment.