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

Owens, Thomas W., Rogers, Renee L., Best, Sarah A., Ledger, Anita, Mooney, Anne-Marie, Ferguson, Alison, Shore, Paul, Swarbrick, Alexander, Ormandy, Christopher J., Simpson, Peter T., Carroll, Jason S., Visvader, Jane E. and Naylor, Matthew J. (2014) Runx2 is a novel regulator of mammary epithelial cell fate in development and breast cancer. Cancer Research, 74 18: 5277-5286. doi:10.1158/0008-5472.CAN-14-0053

Author Owens, Thomas W.
Rogers, Renee L.
Best, Sarah A.
Ledger, Anita
Mooney, Anne-Marie
Ferguson, Alison
Shore, Paul
Swarbrick, Alexander
Ormandy, Christopher J.
Simpson, Peter T.
Carroll, Jason S.
Visvader, Jane E.
Naylor, Matthew J.
Title Runx2 is a novel regulator of mammary epithelial cell fate in development and breast cancer
Journal name Cancer Research   Check publisher's open access policy
ISSN 1538-7445
Publication date 2014-09-15
Year available 2014
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-14-0053
Open Access Status DOI
Volume 74
Issue 18
Start page 5277
End page 5286
Total pages 10
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Collection year 2015
Language eng
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2015 Collection
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Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 11 times in Scopus Article | Citations
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