PTEN expression in U251 glioma cells enhances their sensitivity to ionizing radiation by suppressing DNA repair capacity
H.-L. Li, C.-Y. Wang, J. Fu, X.-J. Yang, Y. Sun, Y.-H. Shao, L.-H. Zhang, X.-M. Yang, X.-L. Zhang, J. Lin Department of Radiotherapy, Shanghai 6th People’s Hospital, Shanghai Jiao Tong University, Shanghai, China. forestsoldier@sohu.com
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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H.-L. Li, C.-Y. Wang, J. Fu, X.-J. Yang, Y. Sun, Y.-H. Shao, L.-H. Zhang, X.-M. Yang, X.-L. Zhang, J. Lin
PTEN expression in U251 glioma cells enhances their sensitivity to ionizing radiation by suppressing DNA repair capacity
Eur Rev Med Pharmacol Sci
Year: 2019
Vol. 23 - N. 23
Pages: 10453-10458
DOI: 10.26355/eurrev_201912_19684