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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
28
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pubmed:dateCreated |
2005-6-30
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pubmed:abstractText |
Transforming growth factor beta1 (TGF-beta1) belongs to a family of polypeptide factors, whose cytostatic and apoptotic functions help restrain the growth of mammalian cells. Although solid data established the role of TGF-beta's as suppressor factors in tumorigenic processes, in the context of an advanced stage of disease, TGF-beta's could also play a pro-oncogenic role. We have previously shown that TGF-beta1 induces both pro- and anti-apoptotic signals in foetal rat hepatocytes. In this work, we have focused on its anti-apoptotic mechanism. We show that TGF-beta1 activates the epidermal growth factor receptor (EGFR) and phosphorylates c-Src. EGFR is required for Akt activation. Blocking EGFR signalling amplifies the apoptotic response to TGF-beta1. TGF-beta1 induced a rapid activation of the tumour necrosis factor-alpha-converting enzyme (TACE/ADAM (a disintegrin and metalloprotease) 17). Inhibitors of TACE considerably attenuated Akt activation, which suggests that TGF-beta1 activates EGF signalling in hepatocytes by promoting shedding of EGF-like ligands. The activation of c-Src by TGF-beta1 is EGFR dependent and is required for full Akt phosphorylation and cell survival. Inhibition of EGFR does not block the epithelial-mesenchymal transition (EMT) induced by TGF-beta1 in hepatocytes, which indicates that activation of EGFR plays an essential role in impairing apoptosis, but it is dispensable for the EMT process.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ADAM Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Akt1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Casp3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Class Ib Phosphatidylinositol...,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Pik3cg protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins pp60(c-src),
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Tgfb1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/tumor necrosis factor-alpha...
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
24
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4580-7
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15856020-ADAM Proteins,
pubmed-meshheading:15856020-Animals,
pubmed-meshheading:15856020-Apoptosis,
pubmed-meshheading:15856020-Caspase 3,
pubmed-meshheading:15856020-Caspases,
pubmed-meshheading:15856020-Cell Survival,
pubmed-meshheading:15856020-Cells, Cultured,
pubmed-meshheading:15856020-Class Ib Phosphatidylinositol 3-Kinase,
pubmed-meshheading:15856020-Epithelial Cells,
pubmed-meshheading:15856020-Hepatocytes,
pubmed-meshheading:15856020-Isoenzymes,
pubmed-meshheading:15856020-Liver,
pubmed-meshheading:15856020-Mesoderm,
pubmed-meshheading:15856020-Metalloendopeptidases,
pubmed-meshheading:15856020-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:15856020-Phosphorylation,
pubmed-meshheading:15856020-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15856020-Proto-Oncogene Proteins,
pubmed-meshheading:15856020-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15856020-Proto-Oncogene Proteins pp60(c-src),
pubmed-meshheading:15856020-Rats,
pubmed-meshheading:15856020-Rats, Wistar,
pubmed-meshheading:15856020-Receptor, Epidermal Growth Factor,
pubmed-meshheading:15856020-Signal Transduction,
pubmed-meshheading:15856020-Transforming Growth Factor beta,
pubmed-meshheading:15856020-Transforming Growth Factor beta1,
pubmed-meshheading:15856020-Tumor Necrosis Factor-alpha
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pubmed:year |
2005
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pubmed:articleTitle |
Involvement of EGF receptor and c-Src in the survival signals induced by TGF-beta1 in hepatocytes.
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pubmed:affiliation |
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid 28040, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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