Pregnancy reprograms the epigenome of mammary epithelial cells and blocks the development of premalignant mammary lesions in response to cMYC-overexpression.

Pregnancy instates a series of cellular and molecular modifications in the mammary epithelial cells (MECs) of the adult female mammary gland. Pregnancy is also known for decreasing the predisposition of rodent and human MECs to oncogenesis. In order to understand the molecular basis for this protective effect, we analyzed the epigenetic changes in the enhancer landscape of murine, post-pregnancy MECs, and their effect on gene regulation, tissue development, and oncogenesis. Using in vivo and in vitro models of normal and malignant mammary development, we found that completion of a pregnancy cycle changed the dynamics of cellular proliferation and gene expression in response to a second wave of pregnancy hormones. Our results also demonstrated that post-pregnancy MECs are resistant to the molecular programs driven by cMYC overexpression, a response that blocked the development of premalignant lesions but did not perturb the pregnancy-induced epigenomic landscape. Citation Format: Mary J. Feigman, Matthew A. Moss, Chen Chen, Samantha L. Cyrill, Michael Ciccone, Marygrace Trousdell, Shih Ting Yang, Wesley D. Frey, John E. Wilkinson, Camila O. dos Santos. Pregnancy reprograms the epigenome of mammary epithelial cells and blocks the development of premalignant mammary lesions in response to cMYC-overexpression [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A09.