Runx2 Is a Novel Regulator of Mammary Epithelial Cell Fate in Development and Breast Cancer
Thomas W Owens, Renee L Rogers, Sarah A Best, Anita Ledger, Anne-Marie Mooney, Alison Ferguson, Paul Shore, Alexander Swarbrick, Christopher J Ormandy, Peter T Simpson, Jason S Carroll, Jane E Visvader, Matthew J Naylor
CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2014
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 addit..View full abstract
Awarded by NHMRC
Awarded by Cancer Research UK
Awarded by National Breast Cancer Foundation
This work was supported by the Australian National Health and Medical Research Council (NHMRC), Cancer Council NSW, Australian Research Council, the Victorian State Government through the Victorian Breast Cancer Research Consortium and Operational Infrastructure Support, and the Australian Cancer Research Foundation. M.J. Naylor and A. Swarbrick were supported by the NHMRC Career Development Fellowships, M.J. Naylor and P. T. Simpson by the National Breast Cancer Foundation of Australia Fellowships, S. A. Best by an NHMRC Postgraduate Scholarship (1017256), C.J. Ormandy by an NHMRC Research Fellowship, and J.E. Visvader by an NHMRC Australia Fellowship.