Growth regulation of two rat adenocarcinoma cell lines by dexamethasone and progesterone

We have studied the effect of steroids on cell proliferation in two continuous cell lines derived from rat mammary tumors induced by 7, 12-dimethyl-benz (a) anthracene (DMBA) and N-nitrosomethylurea (NMU). These cell lines contain high concentrations of glucocorticoid and androgen receptors but no estrogen and progesterone receptors as previously shown (1). The cell proliferation was evaluated by measuring [3H] thymidine incorporation into DNA, cell number, and DNA content. Dexamethasone was found to markedly stimulate cell proliferation in a dose-dependent manner, suggesting that it was acting via the glucocorticoid receptor. The effect of 5 alpha-dihydrotestosterone (DHT) was weaker since a stimulation of [3H] thymidine incorporation was contrasted by the absence of a constant increase of cell proliferation. Progesterone partially stimulated NMU cell growth and totally inhibited the stimulatory effect of dexamethasone in both cell lines. The synthetic progestin R5020 displayed a similar activity to that of progesterone. These results show that progestins can directly modulate the growth of mammary cancer cells even in the absence of progesterone receptor by interacting on the glucocorticoid receptor. We conclude that progestins act mostly as partial agonist-antagonists of glucocorticoids in these two rat mammary adenocarcinoma cell lines.