Loignon M, Fetni R, Gordon A J, Drobetsky E A
Centre de Recherche Guy Bernier, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
Cancer Res. 1997 Aug 15;57(16):3390-4.
Largely on the basis of studies using the potent clastogen ionizing radiation, it has been widely assumed that up-regulation of the cyclin-dependent kinase inhibitor p21(waf1cip1) in cultured cells exposed to DNA-damaging agents is contingent upon the presence of functional p53 tumor suppressor protein. Nevertheless, we demonstrate here that the model mutagen 254-nm UV light induces p21(waf1cip1) protein and concomitant G1 arrest in normal human skin fibroblasts, as well as in p53-deficient fibroblasts derived from cancer-prone Li-Fraumeni syndrome patients. However, as expected, following exposure to ionizing radiation, elevated p21(waf1cip1) protein levels and G1 arrest were observed only in normal fibroblasts. These data provide a prominent and clinically relevant example in which p21(waf1cip1)-mediated growth arrest occurs independently of p53 in human cells treated with a model DNA-damaging agent.
很大程度上基于使用强效染色体断裂剂电离辐射的研究，人们普遍认为，在暴露于DNA损伤剂的培养细胞中，细胞周期蛋白依赖性激酶抑制剂p21（waf1cip1）的上调取决于功能性p53肿瘤抑制蛋白的存在。然而，我们在此证明，模型诱变剂254纳米紫外线在正常人皮肤成纤维细胞以及源自癌症易感李-弗劳梅尼综合征患者的p53缺陷成纤维细胞中诱导p21（waf1cip1）蛋白并伴随G1期阻滞。然而，正如预期的那样，在暴露于电离辐射后，仅在正常成纤维细胞中观察到p21（waf1cip1）蛋白水平升高和G1期阻滞。这些数据提供了一个突出且与临床相关的例子，即在经模型DNA损伤剂处理的人类细胞中，p21（waf1cip1）介导的生长阻滞独立于p53而发生。
