| pubmed-article:16849547 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16849547 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:16849547 | lifeskim:mentions | umls-concept:C0105770 | lld:lifeskim |
| pubmed-article:16849547 | lifeskim:mentions | umls-concept:C0037083 | lld:lifeskim |
| pubmed-article:16849547 | lifeskim:mentions | umls-concept:C0132555 | lld:lifeskim |
| pubmed-article:16849547 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
| pubmed-article:16849547 | lifeskim:mentions | umls-concept:C1710082 | lld:lifeskim |
| pubmed-article:16849547 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:16849547 | lifeskim:mentions | umls-concept:C2911684 | lld:lifeskim |
| pubmed-article:16849547 | lifeskim:mentions | umls-concept:C0185117 | lld:lifeskim |
| pubmed-article:16849547 | pubmed:issue | 14 | lld:pubmed |
| pubmed-article:16849547 | pubmed:dateCreated | 2006-7-19 | lld:pubmed |
| pubmed-article:16849547 | 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. | lld:pubmed |
| pubmed-article:16849547 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16849547 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16849547 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16849547 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:16849547 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16849547 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16849547 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16849547 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16849547 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16849547 | pubmed:month | Jul | lld:pubmed |
| pubmed-article:16849547 | pubmed:issn | 0008-5472 | lld:pubmed |
| pubmed-article:16849547 | pubmed:author | pubmed-author:GellerDavid... | lld:pubmed |
| pubmed-article:16849547 | pubmed:author | pubmed-author:GuoZhongZ | lld:pubmed |
| pubmed-article:16849547 | pubmed:author | pubmed-author:DuQiangQ | lld:pubmed |
| pubmed-article:16849547 | pubmed:author | pubmed-author:ShaoLifangL | lld:pubmed |
| pubmed-article:16849547 | pubmed:author | pubmed-author:HussainS... | lld:pubmed |
| pubmed-article:16849547 | pubmed:author | pubmed-author:HePeijunP | lld:pubmed |
| pubmed-article:16849547 | pubmed:author | pubmed-author:NagashimaMako... | lld:pubmed |
| pubmed-article:16849547 | pubmed:author | pubmed-author:ParkKyung... | lld:pubmed |
| pubmed-article:16849547 | pubmed:author | pubmed-author:SahaiRohitR | lld:pubmed |
| pubmed-article:16849547 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16849547 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:16849547 | pubmed:volume | 66 | lld:pubmed |
| pubmed-article:16849547 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16849547 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16849547 | pubmed:pagination | 7024-31 | lld:pubmed |
| pubmed-article:16849547 | pubmed:dateRevised | 2011-11-2 | lld:pubmed |
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| pubmed-article:16849547 | pubmed:year | 2006 | lld:pubmed |
| pubmed-article:16849547 | pubmed:articleTitle | Regulation of human nitric oxide synthase 2 expression by Wnt beta-catenin signaling. | lld:pubmed |
| pubmed-article:16849547 | pubmed:affiliation | Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. | lld:pubmed |
| pubmed-article:16849547 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:16849547 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
| pubmed-article:16849547 | pubmed:publicationType | Research Support, N.I.H., Intramural | lld:pubmed |
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