Runx2 is a novel regulator of mammary epithelial cell fate in development and breast cancer

Research output: Contribution to journalArticle

  • External authors:
  • Thomas W. Owens
  • Renee L. Rogers
  • Sarah A. Best
  • Anita Ledger
  • Anne Marie Mooney
  • Alison Ferguson
  • Alexander Swarbrick
  • Christopher J. Ormandy
  • Peter T. Simpson
  • Jason S. Carroll
  • Jane E. Visvader
  • Matthew J. Naylor

Abstract

© 2014 American Association for Cancer Research.Regulators of differentiated cell fate can offer targets for managing cancer development and progression. Here, we identify Runx2 as a new regulator of epithelial cell fate in mammary gland development and breast cancer. Runx2 is expressed in the epithelium of pregnant mice in a strict temporally and hormonally regulated manner. During pregnancy, Runx2 genetic deletion impaired alveolar differentiation in a manner that disrupted alveolar progenitor cell populations. Conversely, exogenous transgenic expression of Runx2 in mammary epithelial cells blocked milk production, suggesting that the decrease in endogenous Runx2 observed late in pregnancy is necessary for full differentiation. In addition, overexpression of Runx2 drove epithelial-to-mesenchymal transition-like changes in normal mammary epithelial cells, whereas Runx2 deletion in basal breast cancer cells inhibited cellular phenotypes associated with tumorigenesis. Notably, loss of Runx2 expression increased tumor latency and enhanced overall survival in a mouse model of breast cancer, with Runx2-deficient tumors exhibiting reduced cell proliferation. Together, our results establish a previously unreported function for Runx2 in breast cancer that may offer a novel generalized route for therapeutic interventions.

Bibliographical metadata

Original languageEnglish
Pages (from-to)5277-5286
Number of pages9
JournalCancer Research
Volume74
Issue number18
DOIs
StatePublished - 23 Jul 2014