Role of the functional variant (-652T>G) in the XRCC4 promoter in prostate cancer

Mol Biol Rep. 2014 Nov;41(11):7463-70. doi: 10.1007/s11033-014-3636-1. Epub 2014 Aug 6.

Abstract

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 -652G allele 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • China
  • DNA Primers / genetics
  • DNA-Binding Proteins / genetics*
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Immunohistochemistry
  • Luciferases
  • Male
  • Plasmids / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic / genetics*
  • Prostatic Neoplasms / genetics*
  • Real-Time Polymerase Chain Reaction

Substances

  • DNA Primers
  • DNA-Binding Proteins
  • XRCC4 protein, human
  • Luciferases