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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2003-12-19
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pubmed:abstractText |
Interleukin 6 (IL-6) is a growth and survival factor for multiple myeloma cells. As we report here, the IL-6-dependent human myeloma cell line INA-6 responds with a remarkably rapid and complete apoptosis to cytokine withdrawal. Among the antiapoptotic members of the B-cell lymphoma-2 (Bcl-2) family of apoptosis regulators, only myeloid cell factor-1 (Mcl-1) was slightly induced by IL-6. Overexpression studies demonstrated, however, that IL-6 does not exert its survival effect primarily through this pathway. The IL-6 signal transduction pathways required for survival and the target genes controlled by them were analyzed by using mutated receptor chimeras. The activation of signal transducer and activator of transcription 3 (Stat3) turned out to be obligatory for the survival of INA-6 cells. The same held true for survival and growth of XG-1 myeloma cells. Gene expression profiling of INA-6 cells by using oligonucleotide microarrays revealed many novel IL-6 target genes, among them several genes coding for transcriptional regulators involved in B-lymphocyte differentiation as well as for growth factors and receptors potentially implicated in autocrine or paracrine growth control. Regulation of most IL-6 target genes required the activation of Stat3, underscoring its central role for IL-6 signal transduction. Taken together, our data provide evidence for the existence of an as yet unknown Stat3-dependent survival pathway in myeloma cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokine Receptor gp130,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/IL6ST protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Erythropoietin,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
103
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
242-51
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12969979-Antigens, CD,
pubmed-meshheading:12969979-Apoptosis,
pubmed-meshheading:12969979-Base Sequence,
pubmed-meshheading:12969979-Cell Division,
pubmed-meshheading:12969979-Cell Line, Tumor,
pubmed-meshheading:12969979-Cell Survival,
pubmed-meshheading:12969979-Cytokine Receptor gp130,
pubmed-meshheading:12969979-DNA, Neoplasm,
pubmed-meshheading:12969979-DNA-Binding Proteins,
pubmed-meshheading:12969979-Gene Expression Profiling,
pubmed-meshheading:12969979-Genes, bcl-2,
pubmed-meshheading:12969979-Humans,
pubmed-meshheading:12969979-Interleukin-6,
pubmed-meshheading:12969979-Membrane Glycoproteins,
pubmed-meshheading:12969979-Multiple Myeloma,
pubmed-meshheading:12969979-Mutation,
pubmed-meshheading:12969979-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:12969979-Receptors, Erythropoietin,
pubmed-meshheading:12969979-Recombinant Proteins,
pubmed-meshheading:12969979-STAT3 Transcription Factor,
pubmed-meshheading:12969979-Signal Transduction,
pubmed-meshheading:12969979-Trans-Activators
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pubmed:year |
2004
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pubmed:articleTitle |
Interleukin-6-dependent gene expression profiles in multiple myeloma INA-6 cells reveal a Bcl-2 family-independent survival pathway closely associated with Stat3 activation.
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pubmed:affiliation |
Institute of Clinical Immunology and Transfusion Medicine, University Hospital Leipzig, Johannisallee 30, 04103 Leipzig, Germany. fhorn@medizin.uni-leipzig.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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