Source:http://linkedlifedata.com/resource/pubmed/id/15894558
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2005-8-11
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| pubmed:abstractText |
Interleukin-6 (IL-6) has been identified as an important growth regulator of lung cancer cells. Elevation of serum levels of IL-6 has been found in a subpopulation of lung cancer patients, but rarely in patients with benign lung diseases. Approximately 15% of non-small cell lung cancer (NSCLC) tumors exhibit neuroendocrine (NE) properties (NSCLC-NE) and have been suggested to have the biological characteristics similar to small cell lung cancer (SCLC) with early metastasis and initial responsiveness to chemotherapy. We recently showed that IL-6 promotes cell proliferation and downregulates the expression of neuron-specific enolase (NSE, one of the major NE markers) in NSCLC-NE cells. In this study, we show that IL-6 stimulates a transient increase of tyrosine phosphorylation of STAT3 in a dose-dependent fashion. Inhibition of STAT3 signaling pathway by either AG-490 (JAK2-specific inhibitor) or overexpression of STAT3Y705F (a dominant-negative STAT3) reverses NSE expression in IL-6- treated NSCLC-NE cells. In addition, IL-6 induces phosphorylation and activation of p38 MAPK. SB-203580, a p38 MAPK-specific inhibitor, inhibits IL-6-induced p38 MAPK phosphorylating activity and suppresses IL-6-stimulated cell proliferation. Together, our results indicate that STAT3 signaling pathway is involved in IL-6-induced NE differentiation and that p38 MAPK is associated with IL-6-stimulated growth regulation in NSCLC-NE cells. These data suggest that both kinase pathways play critical roles in the pathogenesis of NSCLC-NE malignancies, providing new molecular targets for future therapeutic approaches.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphopyruvate Hydratase,
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,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
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| pubmed:issn |
1040-0605
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
289
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
L446-53
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| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:15894558-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:15894558-Cell Differentiation,
pubmed-meshheading:15894558-Cell Line, Tumor,
pubmed-meshheading:15894558-Cell Proliferation,
pubmed-meshheading:15894558-DNA-Binding Proteins,
pubmed-meshheading:15894558-Down-Regulation,
pubmed-meshheading:15894558-Enzyme Activation,
pubmed-meshheading:15894558-Humans,
pubmed-meshheading:15894558-Interleukin-6,
pubmed-meshheading:15894558-Lung Neoplasms,
pubmed-meshheading:15894558-Neurosecretory Systems,
pubmed-meshheading:15894558-Phosphopyruvate Hydratase,
pubmed-meshheading:15894558-Phosphorylation,
pubmed-meshheading:15894558-Recombinant Proteins,
pubmed-meshheading:15894558-STAT3 Transcription Factor,
pubmed-meshheading:15894558-Signal Transduction,
pubmed-meshheading:15894558-Trans-Activators,
pubmed-meshheading:15894558-p38 Mitogen-Activated Protein Kinases
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| pubmed:year |
2005
|
| pubmed:articleTitle |
IL-6 induces neuroendocrine dedifferentiation and cell proliferation in non-small cell lung cancer cells.
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| pubmed:affiliation |
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|