KIAA0101 interacts with BRCA1 and regulates centrosome number

Mol Cancer Res. 2011 Aug;9(8):1091-9. doi: 10.1158/1541-7786.MCR-10-0503. Epub 2011 Jun 14.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Centrosome / metabolism*
  • DNA Damage
  • DNA-Binding Proteins
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genomic Instability
  • HeLa Cells
  • Homologous Recombination / genetics
  • Humans
  • Hyaluronan Receptors / metabolism
  • Ki-67 Antigen / analysis
  • RNA, Small Interfering / genetics

Substances

  • BRCA1 Protein
  • Biomarkers, Tumor
  • Carrier Proteins
  • DNA-Binding Proteins
  • Extracellular Matrix Proteins
  • Hyaluronan Receptors
  • Ki-67 Antigen
  • PCLAF protein, human
  • RNA, Small Interfering
  • hyaluronan-mediated motility receptor