Abstract 2400: Identification of histone modifying enzymes associated with tamoxifen resistance in MCF7 breast cancer cells

Abstract

Abstract Tamoxifen is widely used to treat estrogen receptor-alpha positive breast cancer. However, resistance to tamoxifen often prevent the success of endocrine therapy. Epigenetic change in tumors are associated with cancer development and progression. Although altered histone modification has been implicated in tumorigenesis, their role in endocrine resistance was little known. To identified tamoxifen-resistance associated histone methylation modifying enzyme, we examined the global histone H3 methylation patterns in tamoxifen-resistance MCF7 breast cancer cells. Our results show that, the levels of methylated histone H3 lysine 4 (H3K4) and histone H3 lysine 9 (H3K9) was upregulated in tamoxifen resistance MCF7 breast cancer cells. Next, we analysis expression levels of H3K4 and H3K9 methylation modifying enzyme in tamoxifen resistance breast cancer cells. qRT-PCR results show that H3K4 methyltransferases (KMT2A and KMT2C) is upregulated in tamoxifen resistance breast cancer cells. Moreover, we observed that si-RNA mediated knockdown of KMT2C was more susceptible to tamoxifen-induced growth inhibition. Finally, Analyses of publicly available patient data sets indicated that KMT2A and KMT2C levels are higher in patients after endocrine therapy failure (recurrence), compared to those of responders (non-recurrence). Our study indicates that elevated levels of KMT2A and KMT2C in the tamoxifen-resistance breast cancers may contributed tamoxifen resistance. Citation Format: Min-Ho Lee, Mi-Ock Lee. Identification of histone modifying enzymes associated with tamoxifen resistance in MCF7 breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2400. doi:10.1158/1538-7445.AM2017-2400