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

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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Kumar S,Nandi A,Mahesh A,Sinha S,Flores E,Chakrabarti R

doi

10.1002/1873-3468.13703

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

973-985

issue

6

eissn

0014-5793

issn

1873-3468

journal_volume

594

pub_type

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