Functional analysis of promoter variants in KU70 and their role in cancer susceptibility
| Autor: | Jacques Simard, Pauline Cassart, Ekaterini A. Kritikou, Daniel Sinnett, Mathieu Larivière, Manon Ouimet |
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| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Electrophoretic Mobility Shift Assay Biology Polymorphism Single Nucleotide chemistry.chemical_compound Breast cancer Genes Reporter Cell Line Tumor Neoplasms Genetic variation Genetics medicine Humans Electrophoretic mobility shift assay Genetic Predisposition to Disease Allele Promoter Regions Genetic Gene Ku Autoantigen Regulation of gene expression Ku70 Reproducibility of Results Antigens Nuclear medicine.disease DNA-Binding Proteins Gene Expression Regulation Neoplastic chemistry Haplotypes MCF-7 Cells DNA HeLa Cells |
| Zdroj: | Genes, chromosomescancer. 51(11) |
| ISSN: | 1098-2264 |
| Popis: | KU70 is involved in the DNA double-strand break repair pathway, which plays a critical role in maintaining genomic stability and preventing cancer. Genetic variation within the KU70 gene has been shown to be associated with increased risk of several types of cancers including breast cancer. Here, we used gene reporter and gel shift assays combined with site-directed mutagenesis to characterize genetic variation within the KU70 proximal promoter region and investigate the putative functional role of regulatory variation and altered KU70 expression in modulating an individual's susceptibility to disease. We show that the variant rs2267437C>G significantly influences KU70 transcriptional activity in an allele- specific manner and alters DNA-protein complex formation in breast cancer cell lines. Our data provide a possible molecular explanation for the associations observed between the KU70 regulatory variant rs2267437 and breast cancer risk. |
| Databáze: | OpenAIRE |
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