机构：[1]Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China[2]Institute of Neuroscience, Soochow University, Suzhou, China[3]Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, China[4]Department of Surgery, The Third Hospital affiliated to Soochow University, Suzhou, China
We have previously shown that Gai3 is elevated in human glioma, mediating Akt activation and cancer cell proliferation. Here, we imply that Gai3 could also be important for irradiation resistance. In A172 human glioma cells, Gai3 knockdown (by targeted shRNAs) or dominant-negative mutation significantly potentiated irradiation-induced cell apoptosis. Reversely, forced over-expression of wild-type or constitutively-active Gai3 inhibited irradiation-induced A172 cell apoptosis. Irradiation in A172 cells induced Gai3 translocation to cell nuclei and association with local protein DNA-dependent protein kinase (DNA-PK) catalytic subunit. This association was important for DNA damage repair. Gai3 knockdown, depletion (using Gai3 knockout MEFs) or dominant-negative mutation potentiated irradiation-induced DNA damages. On the other hand, expression of the constitutively-active Gai3 in A172 cells inhibited DNA damage by irradiation. Together, these results indicate a novel function of Gai3 in irradiation-resistance in human glioma cells.
基金：
grants from the National Natural Science Foundation of China (Nos. 81302195, 31371139, 81571282, 81502162, 81372411, 81172128); Grants from Natural Science Foundation of Jiangsu Province (BK20130301), and by the Graduate Scientific Research and Innovation Project of Soochow University, KYLX14_1267).
医学