Abstract 943: RRM2: a key contributor in tamoxifen resistance in breast cancer.

Abstract

Abstract Tamoxifen is primarily used for early and advanced ER positive breast cancer patients. Unfortunately about 58% of the patients fail to respond to tamoxifen and eventually relapse with more aggressive tumors. Therefore, understanding the molecular mechanism of resistance is necessary to design new therapeutic strategies to overcome resistance. In this study, we show that Ribonucleotide Reductase M2 subunit is highly expressed in Akt over-expressing breast cancer cell lines and these breast cancer cell lines are highly resistant to tamoxifen treatment In-vitro. In these breast cancer cell lines, RNA interference mediated by small interfering RNA against RRM2 sensitizes these cells to tamoxifen-induced toxicity and reversed the tamoxifen resistance. Also, Using Oncomine database, we demonstrate that RRM2 is overexpressed in breast cancer. This is the first demonstration that investigate role of RRM2 in tamoxifen resistance and could serve as a potential target to restore tamoxifen sensititivity in breast cancer cells. Citation Format: Khyati Niral Shah, David Peterson, Marie Evangelista, Jesika Faridi. RRM2: a key contributor in tamoxifen resistance in breast cancer. [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 943. doi:10.1158/1538-7445.AM2013-943