Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/17963
Título
Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions.
Autor(es)
Fecha de publicación
2003-06-06
Cita
J Biol Chem . 2003 ;278(23):21113-23.
Idioma
Inglés
Tipo de documento
journal article
Resumen
The Snail transcription factor has been described recently as a strong repressor of E-cadherin in epithelial cell lines, where its stable expression leads to the loss of E-cadherin expression and induces epithelial-mesenchymal transitions and an invasive phenotype. The mechanisms regulating Snail expression in development and tumor progression are not yet known. We show here that transforming growth factor beta-1 (TGFbeta1) induces Snail expression in Madin-Darby canine kidney cells and triggers epithelial-mesenchymal transitions by a mechanism dependent on the MAPK signaling pathway. Furthermore, TGFbeta1 induces the activity of Snail promoter, whereas fibroblast growth factor-2 has a milder effect but cooperates with TGFbeta1 in the induction of Snail promoter. Interestingly, TGFbeta1-mediated induction of Snail promoter is blocked by a dominant negative form of H-Ras (N17Ras), whereas oncogenic H-Ras (V12Ras) induces Snail promoter activity and synergistically cooperates with TGFbeta1. The effects of TGFbeta1 on Snail promoter are dependent of MEK1/2 activity but are apparently independent of Smad4 activity. In addition, H-Ras-mediated induction of Snail promoter, alone or in the presence of TGFbeta1, depends on both MAPK and phosphatidylinositol 3-kinase activities. These data support that MAPK and phosphatidylinositol 3-kinase signaling pathways are implicated in TGFbeta1-mediated induction of Snail promoter, probably through Ras activation and its downstream effectors.
MESH
Animals | Cadherins | Cell Line | Cell Movement | DNA-Binding Proteins | Dogs | Epithelial Cells | Fibroblast Growth Factor 2 | Gene Expression | Genes, ras | Kidney | MAP Kinase Kinase 1 | MAP Kinase Kinase 2 | MAP Kinase Signaling System | Mesoderm | Mitogen-Activated Protein Kinase Kinases | Phenotype | Phosphatidylinositol 3-Kinases | Promoter Regions, Genetic | Protein Serine-Threonine Kinases | Protein-Tyrosine Kinases | Snail Family Transcription Factors | Transcription Factors | Transforming Growth Factor beta | Transforming Growth Factor beta1
Descripción
We thank A. Ben-Ze’ev, H. Clevers, T. Gridley, J.
Massague´, P. Rodriguez-Viciana, and M. Takeichi for providing vectors,
genomic clones, and antibodies and M. A. Nieto and M. C. Iglesias for
helpful suggestions and critical reading of the manuscript.
Versión en línea
DOI
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