p53-Independent tumorigenic progression of human prostate cells.

We have previously described the development of radiation transformed human fetal prostate epithelial cells, 267B1. Using this in vitro model system, we investigated the molecular mechanisms of prostate carcinogenic progression by comparing nontumorigenic (267B1/B) and tumorigenic (267B1/D) cells. We examined the G1- to S-phase transition in synchronized cells to determine if the progression of 267B1 cells from nontumorigenic to tumorigenic was the consequence of a perturbation in the G1- to S-phase transition involving p53, pRb, p21, or p16. Nontumorigenic 267B1/B cells showed a time-dependent increase in the expression of p53 and a corresponding increase in p21 following exposure to ionizing radiation (6 Gy). The levels of pRb and p16 protein were virtually unchanged. In contrast, tumorigenic 267B1/D cells exhibited a p53-independent induction of p21 protein with a parallel increase in p16 protein in response to ionizing radiation, but no change in pRb was observed. These results suggest that the progression of 267B1 cells from nontumorigenic to tumorigenic involves p53-independent processes.