title: Hypermethylation and aberrant expression of Wnt-antagonist family genes in gastric cardia adenocarcinoma.
abstract: The canonical Wnt signalling pathway plays a key role during embryogenesis and pathogenesis of various types of tumors. Recently, several studies have shown that the promoter hypermethylation of Wnt-antagonist genes, including sFRP-1, sFRP-2, sFRP-4, sFRP-5, Wif-1 and Dkk-3, have been certified to contribute to the tumorigenesis of several cancers. The aim of this study was to investigate the promoter methylation of Wnt-antagonist genes in gastric cardia adenocarcinoma (GCA) and corresponding adjacent non-cancerous tissues, and to establish the possible relationship between DNA methylation status and the pathogenesis of GCA. MSP, RT-PCR methods were applied respectively to examine the CpG methylation of the Wnt-antagonist genes and its mRNA expression in tumors and corresponding non-cancerous tissues, and immunohistochemistry method was used to determine protein expression of β-catenin(the key factor of the Wnt signalling pathway) and cyclin D1(the target gene of this pathway). The frequency of promoter methylation of sFRP-1, sFRP-2, sFRP-4, sFRP-5, Wif-1 and Dkk-3 genes in GCA tumor tissues were 78.7%(74/94), 76.6%(72/94), 70.2%(66/94), 77.1%(73/94), 61.7%(58/94) and 21.3%(20/94), respectively, which were significantly higher than those in adjacent non-cancerous tissues. Furthermore, the frequencies of silenced mRNA expression of these six genes in GCA tumor tissues were significantly higher than those in adjacent non-cancerous tissues. Methylation levels of these six genes were all correlated with loss of mRNA expression. The ectopic expression of β-catenin and cyclin D1 was significantly more frequent in GCA tumor tissues than that in adjacent non-cancerous tissues and correlated with each Wnt-antagonist genes hypermethylation status. Epigenetic silencing of Wnt-antagonist genes expression by promoter hypermethylation may play an important role in gastric cardia adenocarcinoma.
authors.affiliation: Laboratory of Pathology, Hebei Cancer Insitute, The Fourth Affliliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.forename: W
authors.initials: W
authors.lastname: Guo
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: G
authors.initials: G
authors.lastname: Kuang
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D002299:Cardia; D019938:Cyclin D1 / Q000032:analysis; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D051176:beta Catenin / Q000032:analysis
chemical_list: D012333:RNA, Messenger; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1