UVB-Induced Nuclear Translocation of PTEN Promotes Radiation Sensitivity of Human Malignant Glioma U87MG Cells
Abstract BackgroundPTEN is a tumor suppressor gene, which is often inactivated through mutation and/or deletion in diverse human tumors. In the cytoplasm, PTEN negatively regulates the phosphatidylinositol 3′ kinase (PI3K) signaling pathway, while PTEN also shuttles to the nucleus, where PTEN stabilizes genome and/or participates in DNA repairment after damage. PTEN’s subcellular localization seems to be regulated by various factors. MethodsU87MG cells with expressing Wild-type-PTEN (WT-PTEN) and K13E-PTEN mutant were engineered respectively. The relationship between UV radiation and PTEN’s subcellular localization were elucidated using nuclear and cytosolic fractionation and fluorescence co-localization assay. Related signaling pathways were studied with western blot assays.ResultsHere, we demonstrated that UV irradiation could promote nuclear translocation of both WT-PTEN and K13E-PTEN mutant in a dose-dependent manner, but WT PTEN had a higher level of nuclear accumulation after inducing by UV-irradiation compared to K13E-PTEN. In contrast, the cytoplasmic-nuclear translocation of exogenous PTEN was critical to its tumor-suppressing functions that made U87MG cells more sensitive to the UV irradiation. ConclusionOur findings may have implications for further revealing the function of nuclear PTEN and provide insights for clinical treatment of PTEN-deficient tumors.