BRCA1 has been proposed to be tightly linked to the resistance of tumor cells to ionizing radiation. The pathway leading to this phenomenon is not yet clear. In this work, we investigated the role of BRCA1 in the apop...BRCA1 has been proposed to be tightly linked to the resistance of tumor cells to ionizing radiation. The pathway leading to this phenomenon is not yet clear. In this work, we investigated the role of BRCA1 in the apoptosis regulation in response to carbon ion irradiation. We utilized three different cancer cell lines with various states for BRCA1 and p53 to identify the rela- tionship between endogenous BRCA1 and the apoptosis-related genes, and determine whether p53 function would affect the role of BRCA1 in apoptosis regulation. By Western blot analysis, we found that Bax expressions were not significantly changed after irradiation in all of three cell lines. However, Bcl-2 expression showed an up-regulation by endogenous BRCA1 regardless of p53 status. Moreover, the changes in Bcl-2 protein were due to the increase in the transcriptional levels of Bcl-2 mRNA, based on real-time PCR assay. At the same time, BRCAl-deficient cells showed a greater apoptosis susceptibility to irradiation when compared with BRCAl-proficient cells. The results suggest that BRCA1 might exert p53-independent regulative activities for Bcl-2, which seems account for the low apoptosis susceptibility in BRCAl-proficient carcinomas.展开更多
基金supported by the National Basic Research Program of China (Grant No. 2010CB834202)National Natural Science Foundation of China (Grant Nos. 10835011 and 10805064)+1 种基金Special Foundation of President of the Chinese Academy of Sciencesthe External Cooperation Program of Chinese Academy of Sciences,Japan Society for the Promotion of Science and NIRS for Cooperative Research Program
文摘BRCA1 has been proposed to be tightly linked to the resistance of tumor cells to ionizing radiation. The pathway leading to this phenomenon is not yet clear. In this work, we investigated the role of BRCA1 in the apoptosis regulation in response to carbon ion irradiation. We utilized three different cancer cell lines with various states for BRCA1 and p53 to identify the rela- tionship between endogenous BRCA1 and the apoptosis-related genes, and determine whether p53 function would affect the role of BRCA1 in apoptosis regulation. By Western blot analysis, we found that Bax expressions were not significantly changed after irradiation in all of three cell lines. However, Bcl-2 expression showed an up-regulation by endogenous BRCA1 regardless of p53 status. Moreover, the changes in Bcl-2 protein were due to the increase in the transcriptional levels of Bcl-2 mRNA, based on real-time PCR assay. At the same time, BRCAl-deficient cells showed a greater apoptosis susceptibility to irradiation when compared with BRCAl-proficient cells. The results suggest that BRCA1 might exert p53-independent regulative activities for Bcl-2, which seems account for the low apoptosis susceptibility in BRCAl-proficient carcinomas.
