PTEN公司
张力素
辐射敏感性
DNA修复
癌症研究
Ku70型
DNA损伤
细胞凋亡
辐射灵敏度
抑癌基因
生物
磷酸酶
分子生物学
化学
作者
Hongling Li,Wang Cy,Fu J,Yang Xj,Sun Y,Shao Yh,Zhang Lh,Yang Xm,Zhang Xl,Lin J
标识
DOI:10.26355/eurrev_201912_19684
摘要
Objective Mutations in phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a tumor suppressor gene, lead to altered sensitivity to drugs and radiation in various types of cancer. Restoring PTEN expression in tumor cells can increase radiosensitivity by inhibiting the repair of DNA double-strand breaks (DSBs). Thus, determining the mechanism of action of this protein may lead to novel therapeutic strategies. Materials and methods In this study, we transduced U251 cells with a lentiviral vector expressing PTEN to examine the mechanism of radiosensitization. Specifically, we examined the formation of radiation-induced DNA DSBs and apoptosis, as well as the expression of several proteins involved in repairing DSBs (p53, ataxia-telangiectasia mutated, DNA-dependent protein kinase C, Ku70-80). Results Our results showed that PTEN transduction sensitized U251 cells to X-rays, increasing the number of DSBs per cell and fraction of cells undergoing apoptosis. Additionally, the average size of γH2AX nuclear foci was increased following irradiation. These findings were accompanied by a PTEN-dependent irradiation-independent increase in p53 levels and decrease in phosphorylated Ku70/80 levels. Conclusions Our results suggest that PTEN affects radiosensitivity by reducing DSB repair and by enhancing the p53 pathway, leading to increased apoptosis.
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