Ramsamooj P, Kuettel M, Dritschilo A, Jung M
Department of Radiation Medicine, Georgetown University, Washington, D.C., USA.
Radiat Oncol Investig. 1997;5(6):269-74. doi: 10.1002/(SICI)1520-6823(1997)5:6<269::AID-ROI2>3.0.CO;2-W.
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.
我们之前已经描述了辐射转化的人胎儿前列腺上皮细胞267B1的发育过程。利用这个体外模型系统，我们通过比较非致瘤性（267B1/B）和致瘤性（267B1/D）细胞，研究了前列腺癌发生发展的分子机制。我们检测了同步化细胞从G1期到S期的转变，以确定267B1细胞从非致瘤性转变为致瘤性是否是由于涉及p53、pRb、p21或p16的G1期到S期转变受到干扰所致。非致瘤性267B1/B细胞在暴露于电离辐射（6 Gy）后，p53表达呈时间依赖性增加，p21相应增加。pRb和p16蛋白水平基本不变。相比之下，致瘤性267B1/D细胞在电离辐射后表现出与p16蛋白平行增加的p21蛋白的p53非依赖性诱导，但未观察到pRb的变化。这些结果表明，267B1细胞从非致瘤性到致瘤性的进展涉及p53非依赖性过程。
