Abstract 1130: The role of TET2 in mammary stem cell fate decision

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Abstract Epigenetic mechanisms, including DNA methylation, has an essential role in governing the stem cell fate decision. The Ten-Eleven-Translocation (TET) protein family serves as a primary epigenetic regulator responsible for catalyzing the conversion of the modified genomic base 5-methylcytosine into 5-hydroxymethylcytosine to mediate DNA demethylation. It has been shown that loss of TET2 promotes aberrant stem cell self-renewal in hematopoietic malignancy. Interestingly, our recent study has revealed that expression of TET2 directs the breast cancer stem cell-like population to the differentiation cell fate in vitro. Since aberrant stem cell fate is often associated with tumorigenesis, delineating the role that a critical epigenetic regulator (e.g., TET2) plays to govern the mammary stem cell (MaSC) fate will likely provide new strategies used for breast cancer treatment. Thus, to determine the physiological and pathological roles of TET2 in the regulation of MaSC fate and mammary gland development using a mouse model with mammary specific deletion of the Tet2 gene (MMTV-Cre; Tet2fl/fl). Our data show that deletion of Tet2 in mouse mammary gland leads to disrupted mammary epithelial morphology, defective lobular-alveolar development, along with aberrant mammary stem cell fate decision, contributing to an expansion of the MaSC population and development of mammary lesions. Together, the data demonstrate that TET2 plays an important role in controlling MaSC fate decision to maintain epithelial homeostasis, and loss of TET2 may contribute to the development of mammary malignancies. Citation Format: Meng-Ju Wu, Chun-Ju Chang. The role of TET2 in mammary stem cell fate decision [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1130.