Abstract 3914: IGF-II causes translocation of estrogen receptor beta to the mitochondria in triple negative breast cancer cell lines

Abstract

Abstract Breast cancer is the most frequently diagnosed cancer and is the leading cause of death among women worldwide. Breast cancer is classified by the presence or absence of the estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2). Triple negative breast cancers (TNBCs) lack all 3 receptors and account for approximately 15-20% of all breast cancers. Due to lack of targeted treatments TNBCs become aggressive and can metastasize to other parts of the body. The insulin-like growth factor-II (IGF-II) has an important role in fetal and cancer development. IGF-II signals through the IGF-I receptor (IGF-IR), insulin receptor (Ins-R), and has been associated in cross-talk with the estrogen receptors alpha and beta (ERα, ERß). Our lab has demonstrated that IGF-II activates the translocation of estrogen receptor alpha (ER-α) and estrogen receptor beta (ER-β) in the absence of the estrogen ligand. When co-expressed, ER-β counteracts the proliferative function of ER-α, however the role of ER-β in ER-α negative breast cancers is unclear. Although TNBC accounts for 20% of all BC, 50-90% of all TNBC express high levels of ER-β. Triple negative breast cancer can be more aggressive and difficult to treat. Also, the cancer is more likely to spread and recur. With the elevated levels of expression of the ER-β found in TNBC our lab demonstrated through western blotting and confocal microscopy that not only did treatment with IGF-II increase the expression of ER-β in both ER positive (MCF-7) and TNBC cell lines (CRL-231, 2335, and HS578-T) but it also stimulated translocation predominantly to the mitochondria in the TNBC cell lines. The presence of ER-β in the mitochondria suggests a need for further study on the action of ER-β in the mitochondria of all BC cell lines, especially TNBC cell lines. Citation Format: Chane' O'Bannon-Joseph, Daisy D. DeLeon, Center for Health Disparities and Molecular Medicine. IGF-II causes translocation of estrogen receptor beta to the mitochondria in triple negative breast cancer cell lines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3914. doi:10.1158/1538-7445.AM2015-3914