Source:http://linkedlifedata.com/resource/pubmed/id/15618960
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2005-1-25
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pubmed:abstractText |
Signal transducer and activator of transcription (Stat)3 is constitutively activated in cutaneous T-cell lymphoma (CTCL), where it protects tumour cells against apoptosis. The constitutive activation of Stat3 leads to a constitutive expression of suppressor of cytokine signalling (SOCS)-3. In healthy cells, SOCS-3 is transiently expressed following cytokine stimulation and functions as a negative feedback inhibitor of the Stat3-activating kinases. Here, we attempt to resolve the apparent paradox of a simultaneous SOCS-3 expression and Stat3 activation in the same cells. We show that (i) SOCS-3 expression in tumour cells is equal to or higher than in cytokine-stimulated nonmalignant T cells, (ii) SOCS-3 is not mutated in CTCL, (iii) overexpression of SOCS-3 blocks IFNalpha-mediated growth inhibition without affecting Stat3 activation, growth, and apoptosis, and (iv) inhibition of SOCS-3 by a dominant negative Stat3 (Stat3D) increases the IFNalpha-mediated growth inhibition. Taken together, these data show that SOCS-3 does not inhibit Stat3 activation, growth, and survival in CTCL. In contrast, SOCS3 protects tumour cells against growth inhibition by IFNalpha. Unlike SOCS-1, SOCS-3 is therefore not a tumour suppressor but rather a protector of tumour cells.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SOCS3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Suppressor of Cytokine Signaling...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0887-6924
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
209-13
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15618960-Amino Acid Substitution,
pubmed-meshheading:15618960-Cell Division,
pubmed-meshheading:15618960-Cell Line, Tumor,
pubmed-meshheading:15618960-Humans,
pubmed-meshheading:15618960-Interferon-alpha,
pubmed-meshheading:15618960-Lymphoma, T-Cell,
pubmed-meshheading:15618960-Mutagenesis, Site-Directed,
pubmed-meshheading:15618960-Repressor Proteins,
pubmed-meshheading:15618960-Suppressor of Cytokine Signaling Proteins,
pubmed-meshheading:15618960-Transcription, Genetic,
pubmed-meshheading:15618960-Transcription Factors
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pubmed:year |
2005
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pubmed:articleTitle |
Constitutive SOCS-3 expression protects T-cell lymphoma against growth inhibition by IFNalpha.
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pubmed:affiliation |
Institute of Medical Microbiology and Immunology, Institute of Molecular Biology, University of Copenhagen, Denmark.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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