Role of DeltaNp63gamma in epithelial to mesenchymal transition.
J Biol Chem
; 286(5): 3915-24, 2011 Feb 04.
Article
em En
| MEDLINE
| ID: mdl-21127042
ABSTRACT
Although members of the p63 family of transcription factors are known for their role in the development and differentiation of epithelial surfaces, their function in cancer is less clear. Here, we show that depletion of the ΔNp63α and ß isoforms, leaving only ΔNp63γ, results in epithelial to mesenchymal transition (EMT) in the normal breast cell line MCF10A. EMT can be rescued by the expression of the ΔNp63α isoform. We also show that ΔNp63γ expressed in a background where all the other ΔNp63 are knocked down causes EMT with an increase in TGFß-1, -2, and -3 and downstream effectors Smads2/3/4. In addition, a p63 binding site in intron 1 of TGFß was identified. Inhibition of the TGFß response with a specific inhibitor results in reversion of EMT in ΔNp63α- and ß-depleted cells. In summary, we show that p63 is involved in inhibiting EMT and reduction of certain p63 isoforms may be important in the development of epithelial cancers.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
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Transativadores
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Fator de Crescimento Transformador beta
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Proteínas Supressoras de Tumor
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Proteínas Smad
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Transição Epitelial-Mesenquimal
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article