Epigenetic Silencing of Somatostatin in Gastric Cancer
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Kaya Jackson Mohammed Soutto DunFa Peng TianLing Hu Dana Marshal Wael El-Rifai
- چاپ و سال / کشور: 2010
Description
Background Somatostatin (SST), a primary inhibitor of gastrin-stimulated gastric acid secretion, has potent antitumor and anti-secretory activity in several human cancers. Aims This study was performed to investigate the SST gene expression levels and possible epigenetic mechanisms that regulate expression of SST in gastric adenocarcinomas. Methods Quantitative real-time (RT)-PCR and quantitative bisulfite pyrosequencing were used to study primary gastric cancer tissue samples and cell lines. Results Quantitative RT-PCR analysis revealed downregulation of the SST transcript in 93% of gastric carcinoma samples (30/32), compared with 21 normal samples (P\0.001). Because of the presence of a large CpG island in the SST promoter, we next examined its promoter DNA methylation levels by use of quantitative bisulfite pyrosequencing. The results revealed a significant increase in SST promoter DNA methylation in tumor samples compared with normal samples (P\0.05). Promoter DNA hypermethylation and silencing of SST was also detected in seven gastric cancer cell lines that we tested. To confirm the role of promoter DNA methylation as an epigenetic mechanism regulating SST expression, AGS gastric cancer cells were treated with 5-Aza-dc. This treatment led to reduction of promoter DNA methylation levels of SST accompanied by restoration of its mRNA expression. Conclusions Our results indicate that promoter DNA methylation levels play a critical role in regulating SST expression in gastric cancer. This finding provides a foundation for further studies on the role of SST in gastric carcinogenesis and its potential as a biomarker for gastric cancers.
Dig Dis Sci (2011) 56:125–130 DOI 10.1007/s10620-010-1422-z Received: 14 June 2010 / Accepted: 3 September 2010 / Published online: 7 October 2010
