Stambolic V, MacPherson D, Sas D, Lin Y, Snow B, Jang Y, Benchimol S, Mak T W
Amgen Research Institute and, Ontario Cancer Institute, 620 University Avenue, Ontario, Toronto, Canada.
Mol Cell. 2001 Aug;8(2):317-25. doi: 10.1016/s1097-2765(01)00323-9.
PTEN tumor suppressor is frequently mutated in human cancers and is a negative regulator of PI3'K/PKB/Akt-dependent cellular survival. Investigation of the human genomic PTEN locus revealed a p53 binding element directly upstream of the PTEN gene. Deletion and mutation analyses showed that this element is necessary for inducible transactivation of PTEN by p53. A p53-independent element controlling constitutive expression of PTEN was also identified. In contrast to p53 mutant cell lines, induction of p53 in primary and tumor cell lines with wild-type p53 increased PTEN mRNA levels. PTEN was required for p53-mediated apoptosis in immortalized mouse embryonic fibroblasts. Our results reveal a unique role for p53 in regulation of cellular survival and an interesting connection in tumor suppressor signaling.
PTEN肿瘤抑制因子在人类癌症中经常发生突变，是PI3'K/PKB/Akt依赖的细胞存活的负调节因子。对人类基因组PTEN基因座的研究揭示了PTEN基因上游直接存在一个p53结合元件。缺失和突变分析表明，该元件对于p53诱导的PTEN反式激活是必需的。还鉴定出一个控制PTEN组成型表达的p53非依赖性元件。与p53突变细胞系相反，在具有野生型p53的原代和肿瘤细胞系中诱导p53可增加PTEN mRNA水平。在永生化小鼠胚胎成纤维细胞中，p53介导的细胞凋亡需要PTEN。我们的结果揭示了p53在细胞存活调节中的独特作用以及肿瘤抑制信号传导中一个有趣的联系。
