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 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. Cancer Res; 74(18); 5277-86. ©2014 AACR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Owens TW,Rogers RL,Best S,Ledger A,Mooney AM,Ferguson A,Shore P,Swarbrick A,Ormandy CJ,Simpson PT,Carroll JS,Visvader J,Naylor MJdoi
10.1158/0008-5472.CAN-14-0053subject
Has Abstractpub_date
2014-09-15 00:00:00pages
5277-5286issue
18eissn
0008-5472issn
1538-7445journal_volume
74pub_type
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