J. Biol. Chem., Vol. 259, Issue 2, 1231-1238, Jan, 1984
Dual effects of the progestin R5020 on proteins released by the T47D human breast cancer cells
D Chalbos and H Rochefort
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.