The pattern of -catenin responsiveness within the mammary gland is regulated by progesterone receptor

Experiments involving -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 -catenin signaling has not been investigated. In this study, we demonstrate that activated -catenin rescues alveologenesis in progesterone receptor (PR; Pgr)-null mice during pregnancy. Two distinct subsets of mammary cells respond to expression of N89-catenin. Cells at ductal tips are inherently -catenin-responsive and form alveoli in the absence of PR. However, PR activity confers -catenin responsiveness to progenitor cells along the lateral ductal borders in the virgin gland. Once activated by -catenin, responding cells switch on an alveolar differentiation program that is indistinguishable from that observed in pregnancy and is curtailed by PR signaling.