【摘 要】
：
PTEN (phosphatase and tensin homolog deleted on chromosome 10), a tumor suppressor frequently mutated in human cancer, has various cytoplasmic and nuclear functions.PTEN translocates to the nucleus fr
【机 构】
：
State Key Laboratory of Oncology in South China,Cancer Center,Sun Yat-Sen University,Guangzhou 51006
【出 处】
：
2014医学科学前沿暨第三届个体化治疗与抗肿瘤药物研究新趋向研讨会
论文部分内容阅读
PTEN (phosphatase and tensin homolog deleted on chromosome 10), a tumor suppressor frequently mutated in human cancer, has various cytoplasmic and nuclear functions.PTEN translocates to the nucleus from the cytoplasm in response to oxidative stress.However, the mechanism and function of the translocation are not completely understood.In this study, topotecan, a topoisomerase I inhibitor, and CDDP were employed to induce DNA damage.The results indicate that topotecan or CDDP activates ATM, which phosphorylates PTEN at serine 113 and further regulates PTEN nuclear translocation in A549 and HeLa cells.After nuclear translocation,PTEN induces autophagy, in association with the activation of the p-c-Jun/Sestrin 2/AMPK pathway, in response to topotecan.These results identify PTEN phosphorylation by ATM as essential for PTEN nuclear translocation and the subsequent induction of autophagy in response to DNA damage.
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