癌基因诱导的衰老是抑制肿瘤形成的重要机制之一，许多肿瘤细胞能够抑制这一机制，逃逸衰老进入肿瘤化进程。前期研究中我们发现p53S（p53N236S）杂合的MEF细胞（p53S/+）在H-RasG12V癌基因表达的早期出现衰老表型，而当细胞持续传代后，该细胞能够逃逸衰老并在SCID小鼠体内形成肿瘤，而在p53-/+细胞中则没有这一现象。提示p53S突变能够通过功能获得的方式使细胞逃逸Ras癌基因诱导的衰老并肿瘤化。然而，目前p53突变细胞逃逸Ras癌基因诱导的衰老机制尚不明确。因此，本项目拟通过对已知的逃逸Ras诱导细胞衰老的通路进行检测，同时结合p53S调控下游基因的ChIP-on-Chip和Microarray芯片数据的分析筛选逃逸衰老关键基因，如PGC-1α等，探讨在p53N236S突变的背景下，细胞逃逸Ras诱导衰老继而肿瘤化的机制，为临床上对于该类型肿瘤的治疗策略提供潜在治疗靶点。

The oncogene induced senescence (OIS) is one of the most important mechanisms that inhibit tumor. Numerous tumor cells escape from senescence by dampening OIS and promote tumor progression. Our previous study found the p53S (p53N236S) heterozygous MEF cells (p53S/+), but not p53-/+ cells, emerged senescence phenotypes when H-RasG12V oncogene expression in the early stage, however, after persistent subcultured, these cells overpassed the senescence and formatted tumors in SCID mice. However, the mechanism of the p53 mutant cells escaping from Ras induced senescence remains unclear. Therefore, this project aimed to find the mechanisms of p53N236S mutant cell escaped from Ras induced senescence by checking the well-known Ras induced cell senescence escaping pathway and screening p53S regulated downstream genes detected by ChIP-on-Chip and microarray, such as PGC-1α. To reveal mechanism behind the p53S cells that bypass Ras induced senescence will provide potential targets for clinical treatment of tumors, especially for which are concomitant with OIS escaping phenomenon.