Linked Life Data

14710233

Source:http://linkedlifedata.com/resource/pubmed/id/14710233

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-1-7
pubmed:abstractText
Nonsteroidal anti-inflammatory drugs (NSAIDs) have chemopreventive potential against colorectal carcinomas (CRCs). Inhibition of cyclooxygenase (COX)-2 underlies part of this effect, although COX-2-independent mechanisms may also exist. Nonsteroidal anti-inflammatory drugs appear to inhibit the initial stages of the adenoma-carcinoma sequence, suggesting a link to the APC/beta-catenin/TCF pathway (Wnt-signalling pathway). Therefore, the effect of the NSAID sulindac on nuclear (nonphosphorylated) beta-catenin and beta-catenin/TCF-mediated transcription was investigated. Nuclear beta-catenin expression was assessed in pretreatment colorectal adenomas and in adenomas after treatment with sulindac from five patients with familial adenomatous polyposis (FAP). Also, the effect of sulindac sulphide on beta-catenin/TCF-mediated transcription was studied. Adenomas of FAP patients collected after treatment with sulindac for up to 6 months showed less nuclear beta-catenin expression compared to pretreatment adenomas of the same patients. Sulindac sulphide abrogated beta-catenin/TCF-mediated transcription in the CRC cell lines DLD1 and SW480, and decreased the levels of nonphosphorylated beta-catenin. As a result, the protein levels of the positively regulated TCF targets Met and cyclin D1 were downregulated after sulindac treatment. This study provides in vivo and in vitro evidence that nuclear beta-catenin localisation and beta-catenin/TCF-regulated transcription of target genes can be inhibited by sulindac. The inhibition of Wnt-signalling provides an explanation for the COX-2-independent mechanism of chemoprevention by NSAIDs.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-10223192, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-10449515, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-10449516, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-10555149, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-10562579, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-10738133, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-10815898, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-10910034, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-11057903, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-11259636, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-11313997, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-11713928, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-11751493, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-11756231, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-11874996, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-12234972, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-7576994, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-7657130, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-8052854, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-8298943, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-8299902, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-8385741, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-8694848, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-8707091, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-8859177, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-8861899, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-9192825, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-9336110, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-9738932, http://linkedlifedata.com/resource/pubmed/commentcorrection/14710233-9845279
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0007-0920
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
90
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
224-9
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:14710233-Adenoma, pubmed-meshheading:14710233-Adenomatous Polyposis Coli, pubmed-meshheading:14710233-Adult, pubmed-meshheading:14710233-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:14710233-Cell Nucleus, pubmed-meshheading:14710233-Cell Transformation, Neoplastic, pubmed-meshheading:14710233-Chemoprevention, pubmed-meshheading:14710233-Colorectal Neoplasms, pubmed-meshheading:14710233-Cytoskeletal Proteins, pubmed-meshheading:14710233-Female, pubmed-meshheading:14710233-Humans, pubmed-meshheading:14710233-Mitogens, pubmed-meshheading:14710233-Proto-Oncogene Proteins, pubmed-meshheading:14710233-Signal Transduction, pubmed-meshheading:14710233-Sulindac, pubmed-meshheading:14710233-Trans-Activators, pubmed-meshheading:14710233-Transcription, Genetic, pubmed-meshheading:14710233-Tumor Cells, Cultured, pubmed-meshheading:14710233-Wnt Proteins, pubmed-meshheading:14710233-Zebrafish Proteins, pubmed-meshheading:14710233-beta Catenin
pubmed:year
2004
pubmed:articleTitle
Sulindac targets nuclear beta-catenin accumulation and Wnt signalling in adenomas of patients with familial adenomatous polyposis and in human colorectal cancer cell lines.
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