Abstract 3179: Redox signaling to nuclear respiratory factor-1 proteins by reactive oxygen species contributes to the estrogen-induced breast tumor development

We have investigated the molecular mechanisms by which reactive oxygen species (ROS)-mediated redox signaling regulates estrogen-dependent growth of breast tumorigenesis and prospects for targeting these signaling pathways for therapeutic prevention and control of tumor growth. We present here for the first time that ROS generated by E2 exposure were responsible for in vitro MCF-7 cell tumor formation. This is evident from the inhibition of E2-induced ROS formation by ROS scavengers. H2O2 and O2•− seem to play important role in estrogen-mediated tumor growth redox signaling by inactivation of PTPs, such as, CDC25A, PTEN to prolong signaling through kinases, such as ERK and AKT. We observed a novel link between ROS-generated by estrogen, redox regulation of ERK and AKT-mediated signaling to nuclear regulatory protein, nuclear respiratory factor-1 (NRF-1) and ERα responsive gene expression in breast cancer cells and their involvement in the growth of estrogen-dependent breast tumor. NRF-1 serves as a nucleating factor to recruit signaling proteins involved in regulating estrogen-responsive cell cycle genes, and oxidative stress regulatable proteins. Findings of this study not only identify the new redox signaling pathway critical to the estrogen-dependent growth of breast tumors; but also provides important information for the design of redox signaling based therapeutic agents for the prevention and treatment of breast cancer. Citation Format: Deodutta Roy, Quentin Felty, Victor Okoh. Redox signaling to nuclear respiratory factor-1 proteins by reactive oxygen species contributes to the estrogen-induced breast tumor development. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3179. doi:10.1158/1538-7445.AM2014-3179