Epigenetic alteration of the Wnt inhibitory factor-1 promoter occurs early in the carcinogenesis of Barrett's esophagus.

Détails

ID Serval
serval:BIB_F265334C14AF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Epigenetic alteration of the Wnt inhibitory factor-1 promoter occurs early in the carcinogenesis of Barrett's esophagus.
Périodique
Cancer Science
Auteur(s)
Clément G., Guilleret I., He B., Yagui-Beltrán A., Lin Y.C., You L., Xu Z., Shi Y., Okamoto J., Benhattar J., Jablons D.
ISSN
1349-7006[electronic]
Statut éditorial
Publié
Date de publication
2008
Volume
99
Numéro
1
Pages
46-53
Langue
anglais
Résumé
The role of Wnt antagonists in the carcinogenesis of esophageal adenocarcinoma (EAC) remains unclear. We hypothesized that downregulation of the Wnt inhibitory factor-1 (WIF-1) might be involved in the neoplastic progression of Barrett's esophagus (BE). We analyzed the DNA methylation status of the WIF-1 promoter in normal, preneoplastic, and neoplastic samples from BE patients and in EAC cell lines. We investigated the role of WIF-1 on EAC cell growth and the chemosensitization of the cells to cisplatin. We found that silencing of WIF-1 correlated with promoter hypermethylation. EAC tissue samples showed higher levels of WIF-1 methylation compared to the matched normal epithelium. In addition, we found that WIF-1 hypermethylation was more frequent in BE samples from patients with EAC than in BE samples from patients who had not progressed to EAC. Restoration of WIF-1 in cell lines where WIF-1 was methylation-silenced resulted in growth suppression. Restoration of WIF-1 could sensitize the EAC cells to the chemotherapy drug cisplatin. Our results suggest that silencing of WIF-1 through promoter hypermethylation is an early and common event in the carcinogenesis of BE. Restoring functional WIF-1 might be used as a new targeted therapy for the treatment of this malignancy.
Mots-clé
Adaptor Proteins, Signal Transducing, Adenocarcinoma, Antineoplastic Agents, Barrett Esophagus, Cell Line, Tumor, Cisplatin, DNA Methylation, Disease Progression, Epigenesis, Genetic, Esophageal Neoplasms, Gene Silencing, Humans, Promoter Regions, Genetic, Repressor Proteins
Pubmed
Web of science
Création de la notice
25/06/2008 12:02
Dernière modification de la notice
03/03/2018 22:40
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