rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2005-1-26
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pubmed:abstractText |
Dysregulation of Wnt/beta-catenin pathway plays a central role in early events in colorectal carcinogenesis. We examined the effect of quercetin, a famous anti-tumor agent, against beta-catenin/Tcf signaling in SW480 cells. Quercetin inhibited the transcriptional activity of beta-catenin/Tcf in SW480 and also in HEK293 cells transiently transfected with constitutively active mutant beta-catenin gene, whose product is not induced to be degraded by APC-Axin-GSK3beta complex, so we concluded that its inhibitory mechanism was related to beta-catenin itself or downstream components. To investigate the precise inhibitory mechanism, we performed EMSA showing that binding of the Tcf complexes to its specific DNA-binding sites was strongly suppressed by quercetin. Immunoprecipitation analysis also showed that the binding of beta-catenin to Tcf-4 was also disrupted by quercetin. Western blot analysis proved these decreased bindings resulted from decreased level of beta-catenin and Tcf-4 product in nucleus caused by quercetin. Together, we suggest that quercetin is an excellent inhibitor of beta-catenin/Tcf signaling in SW480 cell lines, and the reduced beta-catenin/Tcf transcriptional activity is due to the decreased nuclear beta-catenin and Tcf-4 proteins.
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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/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Quercetin,
http://linkedlifedata.com/resource/pubmed/chemical/TCF Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/TCF7L2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor 7-Like 2...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-291X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
4
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pubmed:volume |
328
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
227-34
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15670774-Cell Line, Tumor,
pubmed-meshheading:15670774-Cell Nucleus,
pubmed-meshheading:15670774-Colonic Neoplasms,
pubmed-meshheading:15670774-Cytoskeletal Proteins,
pubmed-meshheading:15670774-DNA-Binding Proteins,
pubmed-meshheading:15670774-Dose-Response Relationship, Drug,
pubmed-meshheading:15670774-Humans,
pubmed-meshheading:15670774-Quercetin,
pubmed-meshheading:15670774-Signal Transduction,
pubmed-meshheading:15670774-TCF Transcription Factors,
pubmed-meshheading:15670774-Trans-Activators,
pubmed-meshheading:15670774-Transcription Factor 7-Like 2 Protein,
pubmed-meshheading:15670774-Transcription Factors,
pubmed-meshheading:15670774-beta Catenin
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pubmed:year |
2005
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pubmed:articleTitle |
Quercetin, a potent inhibitor against beta-catenin/Tcf signaling in SW480 colon cancer cells.
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pubmed:affiliation |
Division of Chemistry and Molecular Engineering, Seoul National University, Seoul 151-742, Republic of Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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