Expression of Dnmt1, demethylase, MeCP2 and methylation of tumor-related genes in human gastric cancer.
OBJECTIVE
To explore the effect of DNA methyltransferase, demethylase and methyl-CpG binding protein MeCP2 on the expressions and methylation of hMSH2 and proto-oncogene in human gastric cancer.


METHODS
Paired samples of primary gastric cancer and corresponding para-cancerous, non-cancerous gastric mucosae were obtained from surgically resected specimens of 28 patients. Transcription levels of Dnmt1, 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 Dnmt1 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 hypomethylated c-myc. The transcriptional levels of p16(INK4A) and MeCP2 genes did not display any difference 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.


CONCLUSIONS
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.
Fang
Jing-Yuan
JY
Shanghai Institute of Digestive Disease, Shanghai Second Medical University Renji Hospital, Shanghai 200001, China. jingyuanfang@yahoo.com
Cheng
Zhong-Hua
ZH
Chen
Ying-Xuan
YX
Lu
Rong
R
Yang
Li
L
Zhu
Hong-Yin
HY
Lu
Lun-Gen
LG
D000368:Aged; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005753:Gastric Mucosa / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2; D008875:Middle Aged; D051718:MutS Homolog 2 Protein; D011401:Promoter Regions, Genetic / Q000502:physiology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D014158:Transcription, Genetic
D002868:Chromosomal Proteins, Non-Histone; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012097:Repressor Proteins; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein