Glutamate receptor, ionotropic, kainate 2 silencing by DNA hypermethylation possesses tumor suppressor function in gastric cancer

Chi Sheng Wu, Yen Jung Lu, Hsin Pai Li, Chuen Hsueh, Chang Yi Lu, Yu Wei Leu, Hao Ping Liu, Kwang Huei Lin, Tim Hui Ming Huang, Yu Sun Chang

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Aberrant DNA methylation is considered a major mechanism for silencing tumor suppressor genes in gastric cancer. We used CpG microarray and differential methylation hybridization strategies to identify potential tumor suppressor genes and recovered glutamate receptor, ionotropic, kainate 2 (GRIK2) as a novel epigenetic target in gastric cancer. Additional experiments showed that the promoter region of GRIK2 was hypermethylated in 3 of the 4 tested gastric cancer cell lines, and its expression was restored by treatment of cells with the DNA methylation inhibitor, 5′-aza-dC. In clinical samples, the GRIK2 promoter was differentially hypermethylated in tumor tissues compared with adjacent normal tissues (p < 0.001), and this methylation was inversely correlated with the expression level of GRIK2 mRNA (r = -0.44). Functional studies further showed that GRIK2-expressing gastric cancer cell lines showed decreased colony formation and cell migration. Taken together, these results suggest that GRIK2 may play a tumor-suppressor role in gastric cancer. Future studies are warranted to examine whether DNA hypermethylation of the GRIK2 promoter can be used as a potential tumor marker for gastric cancer.

Original languageEnglish (US)
Pages (from-to)2542-2552
Number of pages11
JournalInternational Journal of Cancer
Volume126
Issue number11
DOIs
StatePublished - Jun 1 2010
Externally publishedYes

Keywords

  • GRIK2
  • Gastric cancer
  • Hypermethylation
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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