RAPAMYCIN-INDUCED APOPTOSIS IS P53-INDEPENDENT IN HUMAN PROSTATE CARCINOMA PC-3 CELLS

We have investigated the mechanisms of rapamycin-induced growth inhibi tion and apoptosis in the PC-3 prostate carcinoma cell line. Rapamycin induced apoptosis as well as the expression of p21(waf1) mRNA and pro tein, independent of p53. Rapamycin treatment also resulted in: a decr ease in cdk2 kinase activity; an increase in hypophosphorylated retino blastoma protein (pRb); a dephosphorylation of p70 S6 kinase; and, gro wth-arrest in G(1)-phase of cell cycle. These data suggest that rapamy cin-induced growth arrest and apoptosis occur through the p53-independ ent induction of p21(waf1). Since this induction occurred soon after r apamycin treatment, possibly, the early induction of p21(waf1) and G(1 )-arrest are important components of the mechanism by which rapamycin induces apoptosis in PC-3 cells.