Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions.
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 ex...
| Autores: | , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2003 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/17963 |
| Acceso en línea: | http://hdl.handle.net/20.500.12105/17963 |
| Access Level: | acceso abierto |
| Palabra clave: | 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 |
| Sumario: | 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. |
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