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Publication : Inducible knockout of ∆Np63 alters cell polarity and metabolism during pubertal mammary gland development.

First Author  Kumar S Year  2020
Journal  FEBS Lett Volume  594
Issue  6 Pages  973-985
PubMed ID  31794060 Mgi Jnum  J:303085
Mgi Id  MGI:6509485 Doi  10.1002/1873-3468.13703
Citation  Kumar S, et al. (2020) Inducible knockout of Np63 alters cell polarity and metabolism during pubertal mammary gland development. FEBS Lett 594(6):973-985
abstractText  The Np63 isoform of the p53-family transcription factor Trp63 is a key regulator of mammary epithelial stem cells that is involved in breast cancer development. To investigate the role of Np63 at different stages of normal mammary gland development, we generated a Np63-inducible conditional knockout (cKO) mouse model. We demonstrate that the deletion of Np63 at puberty results in depletion of mammary stem cell-enriched basal cells, reduces expression of E-cadherin and beta-catenin, and leads to a closed ductal lumen. RNA-sequencing analysis reveals reduced expression of oxidative phosphorylation (OXPHOS)-associated proteins and desmosomal polarity proteins. Functional assays show reduced numbers of mitochondria in the mammary epithelial cells of DeltaNp63 cKO compared to wild-type, supporting the reduced OXPHOS phenotype. These findings identify a novel role for Np63 in cellular metabolism and mammary epithelial cell polarity.
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