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.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Wu CS,Lu YJ,Li HP,Hsueh C,Lu CY,Leu YW,Liu HP,Lin KH,Hui-Ming Huang T,Chang YSdoi
10.1002/ijc.24958subject
Has Abstractpub_date
2010-06-01 00:00:00pages
2542-52issue
11eissn
0020-7136issn
1097-0215journal_volume
126pub_type
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journal_title:International journal of cancer
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