Microarray analysis of gene expression in metastatic gastric cancer cells after incubation with the methylation inhibitor 5-aza-2′-deoxycytidine

While the exact mechanisms involved in cancer metastasis are not fully clarified. the altered expression of many different genes has been reported. Hypermethylation of the promoters of cancer-related genes is often associated with their inacavation during tumorigenesis and may also be involved in metastasis. Here we used cDNA mcroarrays to examine the different gene expression profiles of a primary gastric adenocarcinoma cell line RF1 and its derivative metastasis subline RF48. Compared with RF1, 49 genes were down-regulated and 8 genes were up-regulated in RF48. After treatment of RF48 cell,; with a DNA methylation inhibitor, 5-aza-2-deoxycytidine. 101 genes were up-regulated and 1 gene was down-regulated in treated RF48 when compared with untreated RF48. Comparing gene expression patterns of untreated RF1 untreated RF48 and treated RF48 cells showed 5 genes expressed in RF1 but silenced in RF48, which were reactivated after 5-aza-2'deoxycytidine treatment. Two of those 5 genes have CpG islands within their promoter regions. suggesting that those genes activated by 5-aza-2'-deoxycytidine may result from the direct inhibition of promoter methylation. In conclusion. using global gene expression analysis to-ether with inhibition of DNA methylation, we demonstrate that hvper-methylation of the promoters of certain cancer-related Genes may play a role in cancer metastasis.