The Role of the Progesterone Receptors in Mammary Stem and Progenitor Cell Regulation

Increased exposure to ovarian hormones is strongly linked with breast cancer risk, however, the molecular mechanisms underlying this phenomenon remain poorly understood. The steroid hormone progesterone is highest during the luteal phase of the menstrual cycle and exerts mitogenic effects within specific mammary epithelial cell populations. Specifically, an induction of mammary stem cells (MaSCs) is observed although hormone receptors have not been detected in the MaSC-enriched basal compartment. The progesterone receptor (PR) has two main differentially regulated isoforms, PR A and PR B, but most studies do not distinguish between isoforms. This study identifies a unique PR+ population within the MaSC-enriched basal fraction following progesterone treatment. Further, it is shown that functional PR signaling enriches for HR+ progenitors (CD49b+Sca-1+) within the luminal compartment in addition to inducing total luminal, total basal, and alveolar progenitor activity. Finally, we also identify a previously uncharacterized luminal population (CD49b-Sca-1-) that is progesterone sensitive.M.Sc.2016-03-04 00:00:0