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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 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 wildtype, supporting the reduced OXPHOS phenotype. These findings identify a novel role for ∆Np63 in cellular metabolism and mammary epithelial cell polarity.
This article was published in the following journal.
Name: FEBS letters
Epithelial organization and function depend on coordinated cell polarity. In developing tissues, proliferative epithelia maintain whole tissue polarity as individual cells undergo symmetric divisions....
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To evaluate the effect of the polarity of the electric current in healing.
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Hyperplasia of Mammary Glands is a complex disease, and there is no consensus or guideline for the treatment of this disease. This study was launched to investigate into the problem that w...
The main purpose of this project is to investigate the effects of an exercise program on arterial function and cardiovascular diseases risk factors in obese and lean pre-pubertal children....
A family of proteins that are key components of the WNT SIGNALING PATHWAY, where they function downstream of FRIZZLED RECEPTORS. They contain an N-terminal dishevelled-AXIN PROTEIN (DIX) domain, which mediates oligomerization; a central PDZ DOMAIN which binds to the frizzled receptor; and a C-terminal DEP domain which facilitates binding to the CELL MEMBRANE. Dishevelled proteins have important functions in CELL DIFFERENTIATION and establishing CELL POLARITY.
Tumors or cancer of the MAMMARY GLAND in animals (MAMMARY GLANDS, ANIMAL).
One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.
Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains.
A secreted angiopoietin-like protein expressed under hypoxic conditions by ENDOTHELIAL CELLS. It inhibits cell proliferation, cell migration, and tubule formation; the inactive form accumulates in the endothelial EXTRACELLULAR MATRIX, reducing vascular leakage. ANGPTL4 has direct roles in regulating glucose and lipid metabolism, as well as INSULIN SENSITIVITY, and may also function as a regulator of angiogenesis and tumorigenesis.
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