EFFECT OF RETINOIC ACID ON THE PROLIFERATION AND SECRETORY ACTIVITY OF ANDROGEN-RESPONSIVE PROSTATIC-CARCINOMA CELLS

We studied the effect of retinoic acid on the growth and secretory act ivity of the androgen-responsive prostatic carcinoma cell line LNCaP. Our data showed that retinoic acid at 0.01 muM. stimulated the prolife ration of LNCaP cells but inhibited their growth at 0.1 muM. under and rogen-free conditions. In the presence of 0.1 nM. dihydrotestosterone (DHT), LNCaP cell proliferation was inhibited by 10 muM. retinoic acid but not by lower concentrations of retinoic acid. Retinoic acid reduc ed LNCaP cell growth at concentrations of 0.1 muM. in the presence of 10 nM. DHT. Retinoic acid (10 muM.) also reduced the growth response o f LNCaP cells to epidermal growth factor and transforming growth facto r alpha and potentiated the inhibitory effect of transforming growth f actor beta. In additional studies, retinoic acid induced a dose-depend ent increase in prostate specific antigen (PSA) secretion at concentra tions of 0.1 to 1 muM. Dihydrotestosterone (10 nM.) also enhanced the secretion of PSA by LNCaP cells, and this effect was potentiated in a dose-dependent fashion by the addition of retinoic acid at 0.1-10 muM. Competitive binding studies showed that retinoic acid did not bind to androgen receptors. Overall, retinoic acid had a biphasic effect on L NCaP proliferation and promoted the secretion of PSA. The biphasic eff ect of retinoic acid on LNCaP growth should be considered in designing in vivo studies to determine the impact of retinoic acid on solid pro static tumor growth. In addition, the ability of retinoic acid to incr ease PSA secretion may complicate the interpretation of serum PSA leve ls used for diagnostic and prognostic purposes.