Cell Cycle Regulation in Prostate Cancer and Its Role in the Transition of Androgen-Dependent Prostate Cancer to Androgen-Independency

Abstract

Abstract : Cell proliferation in the prostate is dependent upon androgen and is associated with specific cell cycle alterations. To examine the relation between cell cycle regulation and androgen-induced proliferation in prostate cancer the transferable human prostate tumor MDA Pca 2b was employed. Tumor tissue taken from intact, castrated and castrated, testosterone-treated mice was analyzed by (immuno)histochemistry and western blot. MDA Pca 2b grown in nude mice resembled poorly differentiated tumors. Upon castration cell proliferation decreased, and following androgen replacement cell proliferation increased. No increase in apoptotic rate was observed following androgen deprivation. Following castration no changes were observed in cyclin A, cdk2/4/6, p21 while a decrease in levels of cyclin Dl, cyclin E, p16, p27 and c-myc was detected. P27 and c-myc were also monitored after start of androgen replacement: p27 initially increased to decrease at day 5 on TP; the level of c-myc which was analyzed at days 3 and 5 on TP did not appear to change from the castrated levels. In summary, we observed that in MDA Pca 2b prostate tumors androgen acts primarily on cell proliferation rather than apoptosis which is reflected in the levels of cyclins Dl and E, p16, p27 and c-myc.