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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-8-10
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1532-1827
pubmed:author
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
105
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
552-61
pubmed:dateRevised
2011-9-30
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Repression of KIAA1199 attenuates Wnt-signalling and decreases the proliferation of colon cancer cells.
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
pubmed:publicationType
Journal Article