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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
14
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pubmed:dateCreated |
2000-8-24
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pubmed:abstractText |
Interleukin-9 (IL-9) is a growth factor for T cells and various hematopoietic and lymphoid tumor cells. IL-9 signaling involves activation of Janus kinase (JAK)1 and JAK3 kinases, and signal transducer and activator of transcription (STAT)1, STAT3 and STAT5. Using a dominant negative form of STAT5 (STAT5delta), we demonstrated that this factor is an important mediator of IL-9-dependent Ba/F3 cell growth. Mutation of the STAT binding site of the IL-9 receptor (tyr116phe) results in an important decrease in STAT activation and inhibition of proliferation in the presence of IL-9. A small number of cells escape this inhibition, and IL-9-dependent cell lines could be derived. The selected cells required activation of STAT5 for growth, which was blocked by STAT5delta expression and enhanced by overexpression of wild-type STAT5. In contrast to parental cells, Ba/F3-Phe116 cells growing in the presence of IL-9 further progress to cytokine-independent tumorigenic clones. These tumorigenic clones exhibited a strong cytokine-independent activation of JAK1 and STAT5, which most likely supports their proliferation. Transfection of a constitutively activated variant of STAT5 promoted the growth of wild-type Ba/F3 cells in the absence of cytokine. Finally, the expression of the proto-oncogene pim-1 was correlated with STAT5 activation and cell growth. Our data suggest that STAT5 is an important mediator of IL-9-driven proliferation and that dysregulation of STAT5 activation favors tumorigenesis of lymphoid cells.
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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/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-9,
http://linkedlifedata.com/resource/pubmed/chemical/JAK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/JAK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Jak1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Jak2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Milk Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PIM1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Pim1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-pim-1,
http://linkedlifedata.com/resource/pubmed/chemical/STAT5 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Tetracycline,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0008-5472
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
60
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3971-7
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10919676-Animals,
pubmed-meshheading:10919676-Binding Sites,
pubmed-meshheading:10919676-CHO Cells,
pubmed-meshheading:10919676-Cell Division,
pubmed-meshheading:10919676-Cell Transformation, Neoplastic,
pubmed-meshheading:10919676-Cricetinae,
pubmed-meshheading:10919676-DNA, Complementary,
pubmed-meshheading:10919676-DNA-Binding Proteins,
pubmed-meshheading:10919676-Dose-Response Relationship, Drug,
pubmed-meshheading:10919676-Enzyme Activation,
pubmed-meshheading:10919676-Female,
pubmed-meshheading:10919676-Humans,
pubmed-meshheading:10919676-Interleukin-9,
pubmed-meshheading:10919676-Janus Kinase 1,
pubmed-meshheading:10919676-Janus Kinase 2,
pubmed-meshheading:10919676-Lymphocytes,
pubmed-meshheading:10919676-Mice,
pubmed-meshheading:10919676-Mice, SCID,
pubmed-meshheading:10919676-Milk Proteins,
pubmed-meshheading:10919676-Mutation,
pubmed-meshheading:10919676-Neoplasm Transplantation,
pubmed-meshheading:10919676-Plasmids,
pubmed-meshheading:10919676-Precipitin Tests,
pubmed-meshheading:10919676-Protein Synthesis Inhibitors,
pubmed-meshheading:10919676-Protein-Serine-Threonine Kinases,
pubmed-meshheading:10919676-Protein-Tyrosine Kinases,
pubmed-meshheading:10919676-Proto-Oncogene Proteins,
pubmed-meshheading:10919676-Proto-Oncogene Proteins c-pim-1,
pubmed-meshheading:10919676-STAT5 Transcription Factor,
pubmed-meshheading:10919676-Tetracycline,
pubmed-meshheading:10919676-Time Factors,
pubmed-meshheading:10919676-Trans-Activators,
pubmed-meshheading:10919676-Transfection,
pubmed-meshheading:10919676-Tumor Cells, Cultured
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pubmed:year |
2000
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pubmed:articleTitle |
STAT5 activation is required for interleukin-9-dependent growth and transformation of lymphoid cells.
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pubmed:affiliation |
Ludwig Institute for Cancer Research, Université Catholique de Louvain, Brussels, Belgium. Jean-Baptiste.Demoulin@bru.licr.org
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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