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Please use this identifier to cite or link to this item: http://repository.iitr.ac.in/handle/123456789/20073
Title: Inducible knockout of ∆Np63 alters cell polarity and metabolism during pubertal mammary gland development
Authors: Kumar, Sushil
Nandi A.
Mahesh A.
Sinha S.
Flores E.
Chakrabarti R.
Published in: FEBS Letters
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. © 2019 Federation of European Biochemical Societies
Citation: FEBS Letters, 594(6): 973-985
URI: https://doi.org/10.1002/1873-3468.13703
http://repository.iitr.ac.in/handle/123456789/20073
Issue Date: 2020
Publisher: Wiley Blackwell
Keywords: mammary gland
OXPHOS
polarity
stem cells
∆Np63
ISSN: 145793
Author Scopus IDs: 57213855617
57216244266
57212550808
7403739042
7102222259
16149432900
Author Affiliations: Kumar, S., Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States
Nandi, A., Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States
Mahesh, A., Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States
Sinha, S., Department of Biochemistry, State University of New York, Buffalo, NY, United States
Flores, E., Department of Molecular and Cellular Oncology, Division of Basic Science, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, Department of Molecular Oncology, Cancer Biology and Evolution Program, Moffitt Cancer Center, Tampa, FL, United States
Chakrabarti, R., Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States
Funding Details: We thank Leslie King for critical reading of the manuscript. We thank Penn Vet Comparative Pathology Core for their assistance with embedding and sectioning of formalin-fixed mammary glands. We thank the Flow Cytometry Core at the University of Pennsylvania and Children?s Hospital of Philadelphia (CHOP) for all flow cytometry and sorting-based experiments. We thank Molecular Profiling Core Facility and John Tobias for the RNA-seq data analysis. National Cancer Institute, NCI: R01CA237243
Corresponding Author: Chakrabarti, R.; Department of Biomedical Sciences, United States; email: rumela@vet.upenn.edu
Appears in Collections:Journal Publications [BT]

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