Abstract 509: RNF115/BCA2 E3 ubiquitin ligase promotes breast cancer cell proliferation through targeting p21Waf1/Cip1 for ubiquitin-mediated degradation .

Abstract

Abstract The E3 ubiquitin ligase Ring Finger Protein 115 (RNF115), also known as Breast Cancer Associated gene 2 (BCA2), has previously been reported to be overexpressed in estrogen receptor (ERα) positive breast tumors and to promote breast cell proliferation; however, the mechanism is unknown. In this study, we demonstrated that silencing of BCA2 by siRNA in two ERα-positive breast cancer cell lines MCF7 and T47D decreases cell proliferation and increases the protein levels of the cyclin-dependent kinases inhibitor p21Waf/Cip1. The protein stability of p21 was negatively regulated by BCA2. BCA2 directly interacts with p21 and promotes p21 ubiquitination and proteasomal degradation. Knockdown of p21 partially rescues the cell growth arrest induced by the BCA2 siRNA. These results suggest that BCA2 promotes ERα-positive breast cancer cell proliferation at least partially through down-regulating the expression of p21. This study was supported by National Nature Science Foundation of China (81072162, 81120108019, and U1132605) . Citation Format: Zehua Wang, Arun Seth, Ceshi Chen. RNF115/BCA2 E3 ubiquitin ligase promotes breast cancer cell proliferation through targeting p21Waf1/Cip1 for ubiquitin-mediated degradation . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 509. doi:10.1158/1538-7445.AM2013-509