Cancer Res. 2014 Jul 23. pii: canres.0053.2014.
Owens, TW; Rogers, RL; Best, S; Ledger, A; Mooney, AM; Ferguson, A; Shore, P; Swarbrick, A; Ormandy, CJ; Simpson, PT; Carroll, JS; Visvader, JE; Naylor, MJ
School of Medical Sciences, University of Sydney. Kinghorn Cancer Centre, Garvan Institute of Medical Research, Melbourne. ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research. Faculty of Lifes Sciences, The Universit
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.
The team at Ozgene has over two decades of experience creating customised knockout and knock-in mice for pivotal medical research globally. Over 400 scientific publications are based on research using Ozgene mice.