Poster abstracts

Poster number 22 submitted by Zeina Kais

KIAA0101: a potential biomarker for breast cancer

Zeina Kais (BMI, OSU), Jeffrey Parvin (BMI, OSU)

Abstract:
Inherited predisposition to breast cancer involves mutations in either one of the known breast cancer associated genes, BRCA1 or BRCA2 in about 40% of cases. The search for other “BRCA” genes has not been successful, though there are families with breast cancer predisposition and no known mutation of either BRCA1 or BRCA2. It is possible that the remaining familial cases of breast cancer are due to gene mutations that have low penetrance for the breast cancer phenotype, which complicates their discovery.

To find proteins that collaborate with BRCA1 in the pathogenesis of breast cancer, we analyzed publicly available microarray databases to find genes whose expression is tightly correlated with the levels of expression of BRCA1. Candidate BRCA interactors were then tested using two biological processes regulated by BRCA1: homologous recombination and centrosome duplication. In this study, we focused on KIAA0101, a protein we found to control centrosome numbers and to interact with BRCA1. We analyzed the expression of KIAA0101 in breast cancer tumor samples, and we found that overexpression of KIAA0101 correlated with positive KI67 staining, a biomarker associated with increased disease severity. In addition, since this factor has been shown to be essential for cell survival after UV damage, and since BRCA1 has been shown to be involved in the replication stress repair pathway that is activated after UV damage, we checked the involvement of KIAA0101 in this pathway. Preliminary results show that KIAA0101 is involved in the replication stress response where replication stalling leads to the formation of KIAA0101 nuclear foci. Interestingly, these foci disappear upon depletion of BRCA1 indicating that the two proteins are functioning in the same pathway.

This study proves the significance of using bioinformatics in finding genes/proteins that might function in BRCA1 controlled pathways, and identifies KIAA0101 as a protein that may be important for breast tumorigenesis.

References:
Kais Z, Barsky SH, Mathsyraja H, Zha A, Ransburgh D, He G, Pilarski RT, Shapiro CL, Huang K, and Parvin JD (2011) . KIAA0101 interacts with BRCA1 and regulates centrosome number. Mol Cancer Research 9:1091-9

Keywords: KIAA0101, BRCA1, breast cancer