BRCC36, a Novel Subunit of a BRCA1 E3 Ubiquitin Ligasa Complex: Candidates for BRCA3
Abstract
Breast cancer is a genetically heterogeneous disease, and multiple genes remain to be identified among BRCAl and BRCA2 mutation-negative breast cancer-prone families. We believe that a valid approach to identify genetic factors that contribute to breast cancer risk is to evaluate genes coding for proteins that interact with BRCAl in a multiple protein complex. We have recently found one such candidate, referred to as BRCC36. We have reported a profound increase in BRCC36 expression in breast tumors. Furthermore, our studies have defined BRCC36 as a direct regulator of BRCA1 activation and nuclear foci formation in response to IR in a number of breast cancer cell lines. Our results have found that down-regulation of BRCC36 expression impairs homologous recombination repair (HRR) . Therefore, our data suggest that DNA repair pathway activated in response to IR and appears to sensitize breast cancer cells to IR-induced apoptosis. Importantly, we found that BRCC36 mutated in the germline of a cancer-prone family and may increase the risk of developing breast cancer. Overall, aberrant expression or mutation of BRCC36 genes in breast tumors may lead to disruption of the normal function of BRCAl and contribute to the development of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2007
- Accession Number
- ADA472078
Entities
People
- Xiaowei Chen
Organizations
- Fox Chase Cancer Center