Linked Life Data

15311212

Source:http://linkedlifedata.com/resource/pubmed/id/15311212

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2004-9-16
pubmed:abstractText
E-cadherin is a cell-cell adhesion molecule and tumor invasion suppressor gene that is frequently altered in human cancers. It interacts through its cytoplasmic domain with beta-catenin which in turn interacts with the Wnt (wingless) signaling pathway. We have compared the effects of different tumor-derived E-cadherin variants with those of normal E-cadherin on Wnt signaling and on genes involved in epithelial mesenchymal transition. We established an in-house cDNA microarray composed of 1105 different, sequence verified cDNA probes corresponding to 899 unique genes that represent the majority of genes known to be involved in cadherin-dependent cell adhesion and signaling ('Adhesion/Signaling Array'). The expression signatures of E-cadherin-negative MDA-MB-435S cancer cells transfected with E-cadherin variants (in frame deletions of exon 8 or 9, D8 or D9, respectively, or a point mutation in exon 8 (D370A)) were compared to that of wild-type E-cadherin (WT) transfected cells. From the differentially expressed genes, we selected 38 that we subsequently analyzed by quantitative real-time RT-PCR and/or Northern Blot. A total of 92% of these were confirmed as differentially expressed. Most of these genes encode proteins of the cytoskeleton, cadherins/integrins, oncogenes and matrix metalloproteases. No significant expression differences of genes downstream of the Wnt-pathway were found, except in E-cadherin D8 transfected cells where upregulation of three Tcf/Lef-transcribed genes was seen. One possible reason for the lack of expression differences of the Tcf/Lef-regulated genes is upregulation of SFRP1 and SFRP3; both of which are competitive inhibitors of the Wnt proteins. Interestingly, known E-cadherin transcriptional repressors, such as SLUG (SNAI2), SIP1 (ZEB2), TWIST1, SNAIL (SNAI1) and ZEB1 (TCF8), but not E12/E47 (TCF3), had a lack of upregulation in cells expressing mutated E-cadherin compared to WT. In conclusion, E-cadherin mutations have no influence on expression of genes involved in Wnt-signaling, but they may promote their own expression by blocking upregulation of E-cadherin repressors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0023-6837
pubmed:author
pubmed:issnType
Print
pubmed:volume
84
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1372-86
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15311212-Animals, pubmed-meshheading:15311212-Blotting, Northern, pubmed-meshheading:15311212-Blotting, Western, pubmed-meshheading:15311212-Cadherins, pubmed-meshheading:15311212-Cell Line, Tumor, pubmed-meshheading:15311212-Clone Cells, pubmed-meshheading:15311212-Gene Expression Regulation, Neoplastic, pubmed-meshheading:15311212-Humans, pubmed-meshheading:15311212-Mutation, pubmed-meshheading:15311212-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:15311212-Proto-Oncogene Proteins, pubmed-meshheading:15311212-RNA, Neoplasm, pubmed-meshheading:15311212-Repressor Proteins, pubmed-meshheading:15311212-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15311212-Signal Transduction, pubmed-meshheading:15311212-Transfection, pubmed-meshheading:15311212-Up-Regulation, pubmed-meshheading:15311212-Wnt Proteins
pubmed:year
2004
pubmed:articleTitle
Tumor-associated E-cadherin mutations do not induce Wnt target gene expression, but affect E-cadherin repressors.
pubmed:affiliation
Institute of Pathology, Technical University, Munich, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't