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Original Research Article
p53 regulates epithelial–mesenchymal transition induced by transforming growth factor β†
Article first published online: 20 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 228, Issue 4, pages 801–813, April 2013
How to Cite
Termén, S., Tan, E.-J., Heldin, C.-H. and Moustakas, A. (2013), p53 regulates epithelial–mesenchymal transition induced by transforming growth factor β. J. Cell. Physiol., 228: 801–813. doi: 10.1002/jcp.24229
- Issue published online: 20 DEC 2012
- Article first published online: 20 DEC 2012
- Accepted manuscript online: 27 SEP 2012 07:37AM EST
- Manuscript Accepted: 18 SEP 2012
- Manuscript Received: 9 SEP 2012
- Ludwig Institute for Cancer Research. Grant Number: Uppsala Branch
- Swedish Research Council. Grant Number: K2007-66X-14936-04-3
Epithelial plasticity characterizes embryonic development and diseases such as cancer. Epithelial–mesenchymal transition (EMT) is a reversible and guided process of plasticity whereby embryonic or adult epithelia acquire mesenchymal properties. Multiple signaling pathways control EMT, and the transforming growth factor β (TGFβ) pathway plays a central role as its inducer. Here, we analyzed the role of the tumor suppressor protein p53 in TGFβ-induced EMT in a well-established mammary epithelial cell model. We found that diploid NMuMG mammary cells bi-allelically express a wild type and a missense mutant (R277C) form of p53. Global reduction of both forms of p53 led to an enhanced EMT response to TGFβ. Conversely, stabilization of wild type p53 using the compound nutlin had a negative impact on EMT. After silencing both p53 forms, rescue experiments using either wild type or R277C mutant p53 revealed that wild type p53 inhibited, whereas the R277C mutant did not significantly affect, the TGFβ-driven EMT response. Under serum-free culture conditions, silencing of total p53 levels led to higher numbers of mammospheres characterized by larger size. Rescue of the silenced endogenous p53 with R277C mutant p53, in contrast, suppressed both size and numbers of the mammospheres. This work proposes that wild type p53 controls the efficiency by which mammary epithelial cells undergo EMT in response to TGFβ. J. Cell. Physiol. 228: 801–813, 2013. © 2012 Wiley Periodicals, Inc.