Alterations of the Wnt signaling pathway during the neoplastic progression of Barrett's esophagus.

Details

Serval ID
serval:BIB_C06DCD9273DE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Alterations of the Wnt signaling pathway during the neoplastic progression of Barrett's esophagus.
Journal
Oncogene
Author(s)
Clément G., Braunschweig R., Pasquier N., Bosman F.T., Benhattar J.
ISSN
0950-9232
Publication state
Published
Issued date
2006
Peer-reviewed
Oui
Volume
25
Number
21
Pages
3084-3092
Language
english
Abstract
Aberrant activation of the Wnt signaling pathway has been reported during neoplastic progression in Barrett's esophagus (BE). However, mutations in APC and CTNNB1 genes were rarely observed. In this study, expression pattern of Wnt ligands, Frizzled receptors and APC, as well as the methylation status of the APC, SFRP1 and SFRP2 promoter genes were investigated in normal esophageal mucosa and in preneoplastic and neoplastic lesions of BE patients. Promoter methylation of APC was found in all BE samples and in 95% of esophageal adenocarcinomas (EAC). Full methylation of APC correlated with lack of expression. In EAC, nuclear translocation of beta-catenin was observed regardless of the expression of APC. WNT2 expression was higher in dysplasia and EAC than in BE, with 20/26 (77%) of the EAC showing high expression of WNT2. SFRP1 methylation occurred in all BE samples and in 96% of EAC, while SFRP2 was methylated in 73% of the normal squamous esophageal mucosa samples. In conclusion, (1) alterations of key regulators of the Wnt signaling are frequent in the pathogenesis of BE; (2) the APC and SFRP1 genes are inactivated by promoter methylation in BE; (3) the WNT2 gene is upregulated along the progression from low-grade dysplasia to EAC.
Keywords
Adenocarcinoma, Azacitidine, Barrett Esophagus, Cell Division, Cell Line, Tumor, CpG Islands, DNA Methylation, DNA, Neoplasm, Disease Progression, Esophageal Neoplasms, Gene Expression Regulation, Gene Expression Regulation, Neoplastic, Gene Silencing, Genes, APC, Humans, Intercellular Signaling Peptides and Proteins, Membrane Proteins, Mucous Membrane, Neoplasm Proteins, Precancerous Conditions, Promoter Regions, Genetic, RNA, Messenger, RNA, Neoplasm, RNA, Small Interfering, Signal Transduction, Transfection, Wnt Proteins, Wnt2 Protein, beta Catenin
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2008 19:34
Last modification date
20/08/2019 16:34
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