Epigenetic silencing of somatostatin in gastric cancer

Kaya Jackson, Mohammed Soutto, Dunfa Peng, Tianling Hu, Dana Marshal, Wael El-Rifai

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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 down-regulation 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.

Original languageEnglish (US)
Pages (from-to)125-130
Number of pages6
JournalDigestive Diseases and Sciences
Volume56
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

Keywords

  • Expression
  • Gastric cancer
  • Methylation
  • Somatostatin

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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