Source:http://linkedlifedata.com/resource/pubmed/id/21772334
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2011-8-10
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pubmed:abstractText |
Background:The KIAA1199 transcript is upregulated in colon adenomas and downregulated upon ?-catenin knockdown.Methods:Transcript profiling was performed on >500 colon biopsies, methylation profiling data were compared with transcript data. Immunohistochemistry assessed KIAA1199 protein expression in 270 stage II/III tumours (>3 years follow-up). The effects of stable KIAA1199 knockdown in SW480 cells (three different constructs) were studied using transcriptional profiling, proliferation and protein analysis.Results:The KIAA1199 transcript was strongly upregulated in 95% of adenocarcinomas. Absent expression in normal mucosa correlated with KIAA1199 promotor methylation. Nuclear and cytoplasmic KIAA1199 protein expression was identified in colon adenocarcinomas and other types of cancers. A subpopulation of patients with tumours strongly expressing KIAA1199 in the nucleus showed a better outcome with regard to recurrence as lung or liver metastases. The KIAA1199 knockdown affected the cell cycle and the Wnt-signalling pathway. Reduced cellular proliferation and decreased KI67, phosphorylated retinoblastoma, ?-catenin and ASCL2 protein expression supported these findings. Eighteen Wnt-signalling genes differentially expressed upon KIAA1199 knockdown correlated with the KIAA1199 expression profile in clinical specimens.Conclusion:The KIAA1199 knockdown attenuates the effects of the Wnt/?-catenin signalling and it may thus be regarded as a regulatory part of this pathway.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1532-1827
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
9
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pubmed:volume |
105
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
552-61
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pubmed:dateRevised |
2011-9-30
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pubmed:meshHeading |
pubmed-meshheading:21772334-Adenocarcinoma,
pubmed-meshheading:21772334-Cell Adhesion,
pubmed-meshheading:21772334-Cell Movement,
pubmed-meshheading:21772334-Cell Proliferation,
pubmed-meshheading:21772334-Colorectal Neoplasms,
pubmed-meshheading:21772334-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:21772334-Humans,
pubmed-meshheading:21772334-Immunohistochemistry,
pubmed-meshheading:21772334-Microscopy, Fluorescence,
pubmed-meshheading:21772334-Neoplasm Staging,
pubmed-meshheading:21772334-Protein Array Analysis,
pubmed-meshheading:21772334-Proteins,
pubmed-meshheading:21772334-Signal Transduction,
pubmed-meshheading:21772334-Up-Regulation,
pubmed-meshheading:21772334-Wnt Proteins
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pubmed:year |
2011
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pubmed:articleTitle |
Repression of KIAA1199 attenuates Wnt-signalling and decreases the proliferation of colon cancer cells.
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pubmed:affiliation |
Department of Molecular Medicine MOMA, Center for Molecular Clinical Cancer Research, Aarhus University Hospital/Skejby, DK-8200 Aarhus N, Denmark. kbdr@ki.au.dk, www.mdl.dk
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pubmed:publicationType |
Journal Article
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