Antagonistic roles of Notch and p63 in controlling mammary epithelial cell fates.

Details

Serval ID
serval:BIB_63427FB3E53B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Antagonistic roles of Notch and p63 in controlling mammary epithelial cell fates.
Journal
Cell Death and Differentiation
Author(s)
Yalcin-Ozuysal O., Fiche M., Guitierrez M., Wagner K.U., Raffoul W., Brisken C.
ISSN
1476-5403[electronic], 1350-9047[linking]
Publication state
Published
Issued date
2010
Peer-reviewed
Oui
Volume
17
Number
10
Pages
1600-12
Language
english
Abstract
The breast epithelium has two major compartments, luminal and basal cells, that are established and maintained by poorly understood mechanisms. The p53 homolog, p63, is required for the formation of mammary buds, but its function in the breast after birth is unknown. We show that in primary human breast epithelial cells, maintenance of basal cell characteristics depends on continued expression of the p63 isoform, DeltaNp63, which is expressed in the basal compartment. Forced expression of DeltaNp63 in purified luminal cells confers a basal phenotype. Notch signaling downmodulates DeltaNp63 expression and mimics DeltaNp63 depletion, whereas forced expression of DeltaNp63 partially counteracts the effects of Notch. Consistent with Notch activation specifying luminal cell fate in the mammary gland, Notch signaling activity is specifically detected in mice at sites of pubertal ductal morphogenesis where luminal cell fate is determined. Basal cells in which Notch signaling is active show decreased p63 expression. Both constitutive expression of DeltaNp63 and ablation of Notch signaling are incompatible with luminal cell fate. Thus, the balance between basal and luminal cell compartments of the breast is regulated by antagonistic functions of DeltaNp63 and Notch.Cell Death and Differentiation advance online publication, 9 April 2010; doi:10.1038/cdd.2010.37.
Pubmed
Web of science
Open Access
Yes
Create date
16/07/2010 16:05
Last modification date
20/08/2019 14:19
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