p63 Attenuates Epithelial to Mesenchymal Potential in an Experimental Prostate Cell ModelReportar como inadecuado

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The transcription factor p63 is central for epithelial homeostasis and development. In our model of epithelial to mesenchymal transition EMT in human prostate cells, p63 was one of the most down-regulated transcription factors during EMT. We therefore investigated the role of p63 in EMT. Over-expression of the predominant epithelial isoform ΔNp63α in mesenchymal type cells of the model led to gain of several epithelial characteristics without resulting in a complete mesenchymal to epithelial transition MET. This was corroborated by a reciprocal effect when p63 was knocked down in epithelial EP156T cells. Global gene expression analyses showed that ΔNp63α induced gene modules involved in both cell-to-cell and cell-to-extracellular-matrix junctions in mesenchymal type cells. Genome-wide analysis of p63 binding sites using ChIP-seq analyses confirmed binding of p63 to regulatory areas of genes associated with cell adhesion in prostate epithelial cells. DH1 and ZEB1 are two elemental factors in the control of EMT. Over-expression and knock-down of these factors, respectively, were not sufficient alone or in combination with ΔNp63α to reverse completely the mesenchymal phenotype. The partial reversion of epithelial to mesenchymal transition might reflect the ability of ΔNp63α, as a key co-ordinator of several epithelial gene expression modules, to reduce epithelial to mesenchymal plasticity EMP. The utility of ΔNp63α expression and the potential of reduced EMP in order to counteract metastasis warrant further investigation.

Autor: Jan Roger Olsen, Anne Margrete Oyan, Kari Rostad, Margrete R. Hellem, Jie Liu, Lisha Li, David R. Micklem, Hallvard Haugen, James

Fuente: http://plos.srce.hr/


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