Molecular Cancer Research · 2011 · 74 citations · 36 references
MedicineCancer BiologyOncologyCell DivisionDna RepairMolecular OncologyCancer Cell SignalingCancer Molecular PathologyCell Cycle SignalingCell-cycle DysregulationMolecular Tumor ProfilingBrca1 FunctionCell Cycle DynamicsCentrosome BiologyCentrosome FunctionCentrosome Number ControlMalignant Breast TumorsTissue MicroarraysUv Stress Response
To find genes and proteins that collaborate with BRCA1 or BRCA2 in the pathogenesis of breast cancer, we used an informatics approach and found a candidate BRCA interactor, KIAA0101, to function like BRCA1 in exerting a powerful control over centrosome number. The effect of KIAA0101 on centrosomes is likely direct, as its depletion does not affect the cell cycle, KIAA0101 localizes to regions coincident with the centrosomes, and KIAA0101 binds to BRCA1. We analyzed whether KIAA0101 protein is overexpressed in breast cancer tumor samples in tissue microarrays, and we found that overexpression of KIAA0101 correlated with positive Ki67 staining, a biomarker associated with increased disease severity. Furthermore, overexpression of the KIAA0101 gene in breast tumors was found to be associated with significantly decreased survival time. This study identifies KIAA0101 as a protein important for breast tumorigenesis, and as this factor has been reported as a UV repair factor, it may link the UV damage response to centrosome control.
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