Talk abstracts

Talk on Monday 04:45-05:00pm submitted by Zeina Kais

KIAA0101: a potential biomarker for breast cancer

Zeina Kais (Biomedical Informatics, OSU), Stanford H. Barsky (Department of Pathology, University of Nevada School of Medicine), Haritha Mathsyraja, Alicia Zha, Derek J.R. Ransburgh, ( Biomedical Informatics,OSU), Gang He, Robert T. Pilarski, Charles L. Shapiro, (Department of Pathology, Division of Human Genetics, Department of Hematology / Oncology, OSU), Kun Huang (Biomedical Informatics, OSU), Jeffrey D. Parvin (Biomedical Informatics, OSU)

Abstract:
BRCA1, the breast and ovarian specific tumor suppressor gene, has been shown to be mutated in half of the hereditary breast cancers and epigenetically down-regulated in 14% of sporadic breast cancers. The BRCA1 dependent ubiquitin ligase activity regulates centrosome number in breast derived cell lines and this activity is likely critical for the tumor suppression activity of BRCA1. Other factors might be involved in the regulation of centrosome number but these have yet to be identified. In this study we aim to find genes and proteins that might collaborate with BRCA1 in centrosome regulation using an informatics approach. Depletion of BRCA1 results in supernumerary centrosomes that will cause genomic instability and ultimately might result in tumorigenesis. In my project, we use bioinformatics tools to discover genes that might collaborate with BRCA1 in this phenotype. Using gene expression profiling we identified a list of genes whose expression is tightly correlated with the levels of expression of BRCA1 and BRCA2. Genes from this list were treated as candidates for validation in the lab using RNA interference. Centrosome amplification assays were done in HeLa and Hs578T breast cancer cells where candidate genes were depleted using siRNA or overexpressed with expression plasmids. Then, fluorescent microscopy was used to assay for supernumerary centrosomes. In this study we focus on KIAA0101 a protein we found to interact with BRCA1 and to regulate centrosome number. KIAA0101 expression in breast tumors was elevated as compared to normal and its overexpression correlated with increased severity of the disease and poor survival rates. Controlling centrosome number is a major regulatory step in the prevention of genomic instability, and by being correlated with increased tumor aggressiveeness and poor patient survival rates, KIAA0101 stands out as a potential new prognostic biomarker and a putative therapeutic target for breast cancer.

Keywords: BRCA1, Breast Cancer, KIAA0101