Global Analysis of Methylated Genes in Gastric Cancer by Differential Methylation Hybridization and CpG DNA Microarray and Identification of Glutamate receptor, ionotropic, kainate 2 as a Potential Tumor Suppressor Gene in Gastric Cancer

• Main Authors: Chi Sheng Wu, 吳啟生
• Other Authors: Y. S. Chang
• Format: Others
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/64139597679182429359

博士 === 長庚大學 === 生物醫學研究所 === 98 === Abstract Aberrant DNA methylation is considered as a major mechanism for silencing tumor suppressor genes in gastric cancer. Here, we used CpG microarray and differential methylation hybridization (DMH) 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 revealed that the promoter region of GRIK2 was hypermethylated in three out of the four 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 27 paired tumor tissues compared to 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 revealed 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.