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

Abstract

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 EMT-like changes in normal mammary epithelial cells, while 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 novel function for Runx2 in breast cancer that may offer a novel generalized route for therapeutic interventions.

Type Journal
ISBN 1538-7445 (Electronic) 0008-5472 (Linking)
Authors Owens, T. W.; Rogers, R. L.; Best, S.; Ledger, A.; Mooney, A. M.; Ferguson, A.; Shore, P.; Swarbrick, A.; Ormandy, C. J.; Simpson, P. T.; Carroll, J. S.; Visvader, J. E.; Naylor, M. J.;
Garvan Authors Dr Alex Swarbrick , Prof Chris Ormandy , Dr Matthew Naylor
Publisher Name CANCER RES
Published Date 2014-01-01 00:00:00
URL http://www.ncbi.nlm.nih.gov/pubmed/25056120
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?12418_12774/Cancer Res-2014-Owens-5277-86.pdf