Hypermethylation and aberrant expression of Wnt-antagonist family genes in gastric cardia adenocarcinoma

Rok, strany: 2011, 110 - 117

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. <br />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.<br />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).<br />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.<br />Epigenetic silencing of Wnt-antagonist genes expression by promoter hypermethylation may play an important role in gastric cardia adenocarcinoma. Keywords: Wnt-antagonist genes, DNA methylation, gastric cardiac adenocarcinoma

ISO 690:

Guo, Y., Guo, W., Chen, Z., Kuang, G., Yang, Z., Dong, Z. 2011. Hypermethylation and aberrant expression of Wnt-antagonist family genes in gastric cardia adenocarcinoma. In NEOPLASMA, vol. 58, no.2, pp. 110-117. 0028-2685.

APA:

Guo, Y., Guo, W., Chen, Z., Kuang, G., Yang, Z., Dong, Z. (2011). Hypermethylation and aberrant expression of Wnt-antagonist family genes in gastric cardia adenocarcinoma. NEOPLASMA, 58(2), 110-117. 0028-2685.