The Pattern Of β-Catenin-Responsiveness within the Mammary Gland is Regulated by Progesterone Receptor.
Abstract
Experiments involving β-catenin loss- and gain-of-function in the mammary gland have decisively demonstrated the role of this protein in normal alveologenesis. However, the relationship between hormonal and β-catenin signaling has not been investigated. In this study, we demonstrate that activated β-catenin rescues alveologenesis in progesterone receptor (PR; Pgr)-null mice during pregnancy. Two distinct subsets of mammary cells respond to expression of ΔN89β-catenin. Cells at ductal tips are inherently β-catenin-responsive and form alveoli in the absence of PR. However, PR activity confers β-catenin responsiveness to progenitor cells along the lateral ductal borders in the virgin gland. Once activated by β-catenin, responding cells switch on an alveolar differentiation program that is indistinguishable from that observed in pregnancy and is curtailed by PR signaling.