Source:http://linkedlifedata.com/resource/pubmed/id/16849547
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
14
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| pubmed:dateCreated |
2006-7-19
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| pubmed:abstractText |
Nitric oxide (NO.), an important mediator of inflammation, and beta-catenin, a component of the Wnt-adenomatous polyposis coli signaling pathway, contribute to the development of cancer. We have identified two T-cell factor 4 (Tcf-4)-binding elements (TBE1 and TBE2) in the promoter of human inducible NO synthase 2 (NOS2). We tested the hypothesis that beta-catenin regulates human NOS2 gene. Mutation in either of the two TBE sites decreased the basal and cytokine-induced NOS2 promoter activity in different cell lines. The promoter activity was significantly reduced when both TBE1 and TBE2 sites were mutated (P < 0.01). Nuclear extract from HCT116, HepG2, or DLD1 cells bound to NOS2 TBE1 or TBE2 oligonucleotides in electrophoretic mobility shift assays and the specific protein-DNA complexes were supershifted with anti-beta-catenin or anti-Tcf-4 antibody. Overexpression of beta-catenin and Tcf-4 significantly increased both basal and cytokine-induced NOS2 promoter activity (P < 0.01), and the induction was dependent on intact TBE sites. Overexpression of beta-catenin or Tcf-4 increased NOS2 mRNA and protein expression in HCT116 cells. Lithium chloride (LiCl), an inhibitor of glycogen synthase kinase-3beta, increased cytosolic and nuclear beta-catenin level, NOS2 expression, and NO. production in primary human and rat hepatocytes and cancer cell lines. Treatment with Wnt-3A-conditioned medium increased beta-catenin and NOS2 expression in fetal human hepatocytes. When administered in vivo, LiCl increased hepatic beta-catenin level in a dose-dependent manner with simultaneous increase in NOS2 expression. These data are consistent with the hypothesis that beta-catenin up-regulates NOS2 and suggest a novel mechanism by which the Wnt/beta-catenin signaling pathway may contribute to cancer by increasing NO. production.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Lithium Chloride,
http://linkedlifedata.com/resource/pubmed/chemical/NOS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/TCF Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/TCF7L2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tcf7l2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor 7-Like 2...,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0008-5472
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
66
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
7024-31
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| pubmed:dateRevised |
2011-11-2
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| pubmed:meshHeading |
pubmed-meshheading:16849547-Animals,
pubmed-meshheading:16849547-Cell Line, Tumor,
pubmed-meshheading:16849547-Glycogen Synthase Kinase 3,
pubmed-meshheading:16849547-HCT116 Cells,
pubmed-meshheading:16849547-Humans,
pubmed-meshheading:16849547-Lithium Chloride,
pubmed-meshheading:16849547-Liver,
pubmed-meshheading:16849547-Male,
pubmed-meshheading:16849547-Nitric Oxide Synthase Type II,
pubmed-meshheading:16849547-Promoter Regions, Genetic,
pubmed-meshheading:16849547-RNA, Messenger,
pubmed-meshheading:16849547-Rats,
pubmed-meshheading:16849547-Rats, Inbred Lew,
pubmed-meshheading:16849547-Signal Transduction,
pubmed-meshheading:16849547-TCF Transcription Factors,
pubmed-meshheading:16849547-Transcription Factor 7-Like 2 Protein,
pubmed-meshheading:16849547-Transcriptional Activation,
pubmed-meshheading:16849547-Transfection,
pubmed-meshheading:16849547-Wnt Proteins,
pubmed-meshheading:16849547-beta Catenin
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| pubmed:year |
2006
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| pubmed:articleTitle |
Regulation of human nitric oxide synthase 2 expression by Wnt beta-catenin signaling.
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| pubmed:affiliation |
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural,
Research Support, N.I.H., Intramural
|