RANK Signaling Amplifies WNT-Responsive Mammary Progenitors through R-SPONDIN1.

ABSTRACT: Systemic and local signals must be integrated by mammary stem and progenitor cells to regulate their cyclic growth and turnover in the adult gland. Here, we show RANK-positive luminal progenitors exhibiting WNT pathway activation are selectively expanded in the human breast during the progesterone-high menstrual phase. To investigate underlying mechanisms, we examined mouse models and found that loss of RANK prevents the proliferation of hormone receptor-negative luminal mammary progenitors and basal cells, an accompanying loss of WNT activation, and, hence, a suppression of lobuloalveologenesis. We also show that R-spondin1 is depleted in RANK-null progenitors, and that its exogenous administration rescues key aspects of RANK deficiency by reinstating a WNT response and mammary cell expan

SUBMITTER: Joshi PA 

PROVIDER: S-EPMC4618445 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature