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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-10-24
pubmed:abstractText
Invasion of colorectal carcinomas (CC) is characterized by nuclear accumulation of beta-catenin, a key component of the Wnt pathway, in scattered tumor cells. beta-catenin acts in cooperation with T-cell factor (Tcf) HMG-box transcription factors as a transcriptional activator of genes involved in tumor progression. Overexpression of CD97, a molecule that correlates with dedifferentiation and tumor stage in CC, parallels to nuclear translocation of beta-catenin. Here, we investigated whether CD97 is a direct beta-catenin/Tcf target gene. SW480 CC cells were used to mimic the phenotypical switch between central and invasive tumor areas. We demonstrate two-fold higher CD97 expression and nuclear beta-catenin accumulation in cells grown at low density compared to cells cultured at high density, showing membrane-associated beta-catenin. This suggests that CD97 expression correlates with the cellular localization of beta-catenin. However, CD97 mRNA expression levels were not affected by Tcf-1 or Tcf-4 as determined in inducible dominant-negative (dn) Tcf CC cell lines. Furthermore, co-expression of wildtype (wt) or S33A mutated beta-catenin with Tcf-4 did not influence CD97 promoter activity. Inhibition of glycogen synthase kinase (GSK)-3beta, a negative regulator of the canonical Wnt pathway, had no influence on CD97 expression levels. In summary, enhanced CD97 expression in CC cells is regulated independent of beta-catenin/Tcf-4, and is thus not a direct target of the canonical Wnt pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0899-1987
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
881-6
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
CD97 overexpression in tumor cells at the invasion front in colorectal cancer (CC) is independently regulated of the canonical Wnt pathway.
pubmed:affiliation
Department of Surgery, Research Laboratories, The University of Leipzig, Leipzig, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't