Regulation of DNA methylation on expression of genes in human gastric cancer cell lines

Background: The aberrant methylation is associated with the development of gastric cancer. In recent years the methylation has been a hot spot in cancer research. Aims: To investigate the effects of DNA methylation on tumor suppressor genes, oncogenes and apoptosis-associated genes in different human gastric cancer cell lines by DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine (5-aza-dC) intervention, and to detect the changes of cell cycle by using flow cytometry. Methods: Three gastric cancer cell lines (MKN-45, MKN-28 and HGC-27) were treated with 5-aza-dC in different concentrations. The expression of p16INK4A, p2lWAF1, p73, c-myc, c-Ha-ras, survivin and death-associated protein kinase (DAP-kinase) genes were assayed by reverse transcriptase polymerase chain reaction (RT-PCR). Cell cycle was analyzed by flow cytometry. Results: Tumor suppressor gene p16INK4A expression was detected in MKN-45 and HGC-27 cells. The expression of pl6INK4A was obviously up-regulated at either 10 μmol/L of 5-aza-dC for 24 hours or other concentrations for 72 hours, and 5 μmol/L or 10 μmol/L for 24 hours, in MKN-45 and HGC-27 cells, respectively. However, p21WAF1 and p73 gene's transcription levels were not changed, so did the oncogenes c-myc and c-Ha-ras. survivin, an apoptosis-associated gene's expression was increased at MKN-45 cell, but DAP-kinase gene had no significant change at HGC-27 cell. Conclusions: The effects of DNA methylation on tumor suppressor genes, oncogenes and apoptosis-associated genes in different human cancer cell lines are quite distinct. The expression of p16INK4A and survivin genes can be regulated by DNA methylation in MKN-45 and HGC-27 cells, and MKN-45 cell respectively, but not MKN-28.