The Pattern Of β-Catenin-Responsiveness within the Mammary Gland is Regulated by Progesterone Receptor.

Minoti Hiremath, Boise State University
John Lydon, Baylor College of Medicine
Pamela Cowin, New York University School of Medicine


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.