| Bcr-Abl activates the AKT/Fox O3 signalling pathway to restrict transforming growth factor-beta-mediated cytostatic signals. | |
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MedLine Citation:
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PMID: 16113647 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The fusion of Abl with either Bcr or Tel in human leukaemia leads to the constitutive activation of Abl tyrosine kinase, which in turn induces growth-factor-independent proliferation and cell survival. However, the mechanism by which Bcr-Abl induces cellular transformation has not yet been well characterized. Here, we show that Bcr-Abl-expressing cells are resistant to growth inhibition and apoptosis mediated by transforming growth factor-beta (TGF-beta). Interestingly, we observed that the suppressive effects of Bcr-Abl on TGF-beta responses were not mediated by an impairment of Smad signalling, which is believed to act as the principal mediator of TGF-beta responses. In contrast, we found that Bcr-Abl can target the protein kinase AKT and the transcription factor Fox O3 to interfere with growth inhibition and apoptosis in response to TGF-beta. Our results show a novel mechanism of cellular transformation by the oncogenic fusion protein Bcr-Abl through suppression of the cytostatic actions of TGF-beta. |
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Authors:
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Azeddine Atfi; Lucile Abécassis; Marie-Francoise Bourgeade |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: EMBO reports Volume: 6 ISSN: 1469-221X ISO Abbreviation: EMBO Rep. Publication Date: 2005 Oct |
Date Detail:
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Created Date: 2005-10-13 Completed Date: 2006-01-31 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 100963049 Medline TA: EMBO Rep Country: England |
Other Details:
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Languages: eng Pagination: 985-91 Citation Subset: IM |
Affiliation:
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INSERM U482, 184 Rue du Faubourg St-Antoine, 75571 Paris, France. atfi@st-antoine.inserm.fr |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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physiology Animals Apoptosis Blotting, Western Cell Line Cell Proliferation Fluorescent Antibody Technique Forkhead Transcription Factors / physiology* Fusion Proteins, bcr-abl / physiology* Humans Mice Phosphorylation Proto-Oncogene Proteins c-akt / physiology* Signal Transduction / physiology* Transforming Growth Factor beta / biosynthesis, physiology* |
| Chemical | |
Reg. No./Substance:
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0/Forkhead Transcription Factors; 0/Fusion Proteins, bcr-abl; 0/Transforming Growth Factor beta; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
| Comments/Corrections | |
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