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FEBS Lett. 2019 Dec 3. doi: 10.1002/1873-3468.13703. [Epub ahead of print]

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

Author information

1
Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
2
Department of Biochemistry, State University of New York, Buffalo, NY, USA.
3
Department of Molecular and Cellular Oncology, Division of Basic Science, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
4
Department of Molecular Oncology, Cancer Biology and Evolution Program, Moffitt Cancer Center, Tampa, FL, USA.

Abstract

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 β-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 ΔNp63 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.

KEYWORDS:

OXPHOS; mammary gland; polarity; stem cells; ∆Np63

PMID:
31794060
DOI:
10.1002/1873-3468.13703

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