Dual effects of the progestin R5020 on proteins released by the T47D human breast cancer cells

Abstract

R5020, a synthetic progestin, regulates the production of [35S]methionine-labeled proteins released into the medium by T47D human breast cancer cells in culture, as measured by trichloroacetic acid precipitation and dodecyl hydrogen sulfate sodium salt-polyacrylamide gel electrophoresis. Two contrasting responses were observed: (a) a rapid and specific accumulation in the medium of a newly synthesized protein of molecular weight 48,000 and (b) a subsequent general inhibition of the release of proteins within the first 6 days of treatment while the cell number was not altered. These responses were triggered by physiologically active concentrations of progestins (progesterone, R5020, medroxyprogesterone acetate) but not by other classes of steroids, and were not observed in a progesterone receptor negative cell line (BT20), indicating that they were mediated by the progesterone receptor. A progestin antagonist, RU38,486, inhibited the production of the 48-kilodalton released protein. The production of androgen-regulated proteins (43 kilodaltons, 18 kilodaltons) was also increased by dihydrotestosterone and higher concentrations of R5020. These results show that progestins specifically regulate the production of proteins in cell culture. Subsequently, R5020 also inhibit the growth of T47D cells in the presence of estradiol (Vignon, F., Bardon, S., Chalbos, D., and Rochefort, H. (1983) J. Clin. Endocrinol. Metab. 56, 1124-1130), suggesting that the proteins released into the medium may be related to the control of cell proliferation.