Accession Number : ADA486526


Title :   BRCC36, a Novel Subunit of a BRCA1 E3 Ubiquitin Ligase Complex: Candidates for BRCA3


Descriptive Note : Final rept. 15 May 2004-14 May 2008


Corporate Author : FOX CHASE CANCER CENTER PHILADELPHIA PA


Personal Author(s) : Chen, Xiaowei


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a486526.pdf


Report Date : Jun 2008


Pagination or Media Count : 66


Abstract : Breast cancer is a genetically heterogeneous disease, and multiple genes remain to be identified among BRCA1 and BRCA2 mutation-negative breast cancer-prone families. We hypothesized that other proteins, which have equivalent or complementary functions as BRCA1, may also be involved in the development of breast cancer. We have recently found one such candidate, referred to as BRCC36. We have reported a profound increase in BRCC36 expression in breast tumors which leads to tumorigenesis in vitro. 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 BRCA1 and contribute to the development of breast cancer.


Descriptors :   *MUTATIONS , *BREAST CANCER , GENES , DEOXYRIBONUCLEIC ACIDS , PROTEINS


Subject Categories : Genetic Engineering and Molecular Biology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE