Abstract 1005: Tamoxifen treatment induces the epigenetic changes in breast cancer stem cells

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Abstract Purpose: Breast cancer is diagnosed in younger women population and is the leading cause of cancer-related deaths in India. Tamoxifen (TOM) is one of the most effective and widely used first-line endocrine therapy for ER+ breast cancer. However, breast cancer patients often develop TOM resistance and enhanced with caner stem cell (CSC)-like phenotypes. These TOM-resistance (TR) breast cancer phenotypes are highly aggressive and they do not respond to most of the chemotherapies. It is therefore essential to understand the mechanism that resulted in the development of TR in breast cancer. The current study was designed to investigate the epigenetic changes associated mechanism that induces the development of hormone-resistance in breast CSCs. Experimental Procedure: In this study, we used ALDEFLOUR assay, flow cytometry, mammosphere culture, western blot, Chromatin-immunoprecipitation, and RT-PCR analyses. Results: Our study showed that breast CSC-like population possesses higher TR cancer cell phenotypes than non-CSCs. We generated MCF7-derived mammospheres (CSCs) utilizing MammoCult media. However, when treated with TOM (1µM)-we observed an increased number of mammospheres (CSCs) than vehicle control. We found a strong interplay between TR and epigenetic changes, in particular, the changes observed in histone demethylase, which is believed to be one of the crucial links that involved in the development of therapy resistance and enhanced CSC population. Furthermore, TR breast CSCs derived from MCF7 cells display an increased expression of the NOTCH-1 protein. Induced overexpression of NOTCH in MCF7 cells increased the number of mammosphere formation ability than control cells. Finally, overexpression of NOTCH-1 also led to transcriptional up-regulation of cyclin genes A, B, and D. Conclusion: We observed a crucial interplay between TR and breast CSCs. TR associated epigenetic alteration enhanced the expression of NOTCH1, which resulted in increased mitotic signals in the tumor cells including CSCs. Thus, these new phenotypes of breast CSCs with TR characteristics need more understanding for the development of effective combinatorial and adjuvant therapies. Note: This abstract was not presented at the meeting. Citation Format: Kanagarj Palaniyandi, Dhanavathy Gnasampandapandian, Ilangovan Ramachandran, Yuvaraj Sambandam, Parthasarathy Chandrakesan. Tamoxifen treatment induces the epigenetic changes in breast cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1005.