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. |