期刊
MOLECULAR BIOLOGY REPORTS
卷 41, 期 11, 页码 7463-7470出版社
SPRINGER
DOI: 10.1007/s11033-014-3636-1
关键词
XRCC4; EMSA; Prostate cancer
资金
- National Natural Science Foundation of China [81272831, 81202034]
- Jiangsu Province's Outstanding Medical Academic Leader program [RC201178]
- Six-Kinds-of-Top-Talent Program of Jiangsu Province
- Science Foundation of Benq Medical Center [SRD20100004]
Several genes encoding DNA repair molecules have been proposed as cancer-susceptibility genes. Many studies have suggested that SNPs in XRCC4 could be implicated in altering the risk of prostate cancer (PCa). We examined the role of the functional variant (-652T>G) in the XRCC4 promoter in PCa. The transcriptional activity of XRCC4 gene was measured by luciferase assay. We performed real-time PCR/immunohistochemical assay to verify the association between expression level of XRCC4 mRNA/protein and XRCC4 -652T>G polymorphism. In addition, electrophoretic mobility shift assay (EMSA) was used to confirm whether this polymorphism has an effect on binding ability of the transcription factor. We found that the G variant significantly increased the transcription activity of the XRCC4 gene and the binding ability of transcriptional factor GATA-1 to the XRCC4 promoter. Furthermore, the results suggested that the XRCC4 protein and mRNA were overexpressed in individuals who carried the-652 Gallele compared to carriers of the -652T allele. In addition, the expression of XRCC4 in PCa tissues was lower than in adjacent normal tissues. Our data suggest that the XRCC4 promoter -652G>T polymorphism is functional and may influence genetic susceptibility to prostate cancer. Case-control studies are required to validate our findings in the future.
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