AIM: To explore the effect of DNA methyltransferase,demethylase and methyl-CpG binding protein MeCP2 on the expressions and methylation of hMSH2 and protooncogene in human gastric cancer.METHODS: Paired samples of pri...AIM: To explore the effect of DNA methyltransferase,demethylase and methyl-CpG binding protein MeCP2 on the expressions and methylation of hMSH2 and protooncogene in human gastric cancer.METHODS: Paired samples of primary gastric cancer and corresponking para-cancerous, non-cancerous gastric mucosae were obtained from surgically resected specimens of 28 patients. TranscriplJon levels of Dnmtl, mbd2, MeCP2, p16^INK4A,hMSH2 and c-myc were detected by using real-time PCR or RT-PCR. Promoter methylation of p16^INK4A, c-myc and hMSH2 genes was assayed by methylation-specific PCR (MSP) and sequencing (mapping). Their relationships were analyzed by Fisher's exact test using the software SPSS.RESULTS: The average mRNA level of Dnmtl gene from cancerous tissue was higher and that of mbd2 gene from cancerous tissue was lower than that from non-cancerous tissue, respectively, mbd2 was lower in cancerous tissue than in non-cancerous tissue in 14 (50.0%) of patients but higher in 3 cases (10.7%) of non-cancerous gastric tissue(P<0.001). c-myc expression was up-regulated in cancer tissues (P<0.05). The up-regulation of mbd2 was found in all patients with hypomethyiated c-myc. The transcriptional levels of p16^IK4A and MeCP2 genes did not display any differenoe between gastric cancerous and matched non-cancerous tissues. There were down-regulation and hypermethylation of hMSH2 in cancer tissues, and the hypermethylation of hMSH2 coexisted with down-regulated transcription.However, the transcription level of the above genes was not associated with biological behaviours of gastric cancers.CONCLUSION: The up-regulation of proto-oncogene may be the consequence of epigenetic control of gene expression by demethylase, and mbd2 is involved in the regulation of hMSH2 expression in human gastric cancer.展开更多
基金Supported by National Natural Science Foundation of China,No.30170413Foundation for the Author of National Excellent Doctoral Dissertation of China,No.199946 and the Key Project Funds of Shanghai Education Committee
文摘AIM: To explore the effect of DNA methyltransferase,demethylase and methyl-CpG binding protein MeCP2 on the expressions and methylation of hMSH2 and protooncogene in human gastric cancer.METHODS: Paired samples of primary gastric cancer and corresponking para-cancerous, non-cancerous gastric mucosae were obtained from surgically resected specimens of 28 patients. TranscriplJon levels of Dnmtl, mbd2, MeCP2, p16^INK4A,hMSH2 and c-myc were detected by using real-time PCR or RT-PCR. Promoter methylation of p16^INK4A, c-myc and hMSH2 genes was assayed by methylation-specific PCR (MSP) and sequencing (mapping). Their relationships were analyzed by Fisher's exact test using the software SPSS.RESULTS: The average mRNA level of Dnmtl gene from cancerous tissue was higher and that of mbd2 gene from cancerous tissue was lower than that from non-cancerous tissue, respectively, mbd2 was lower in cancerous tissue than in non-cancerous tissue in 14 (50.0%) of patients but higher in 3 cases (10.7%) of non-cancerous gastric tissue(P<0.001). c-myc expression was up-regulated in cancer tissues (P<0.05). The up-regulation of mbd2 was found in all patients with hypomethyiated c-myc. The transcriptional levels of p16^IK4A and MeCP2 genes did not display any differenoe between gastric cancerous and matched non-cancerous tissues. There were down-regulation and hypermethylation of hMSH2 in cancer tissues, and the hypermethylation of hMSH2 coexisted with down-regulated transcription.However, the transcription level of the above genes was not associated with biological behaviours of gastric cancers.CONCLUSION: The up-regulation of proto-oncogene may be the consequence of epigenetic control of gene expression by demethylase, and mbd2 is involved in the regulation of hMSH2 expression in human gastric cancer.
