Expression of Dnmt1, demethylase, MeCP2 and methylation of tumor-related genes in human gastric cancer.

Abstract

AIM:

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.

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.

• Authors: Jing-Yuan Fang, Zhong-Hua Cheng, Ying-Xuan Chen, Rong Lu, Li Yang, Hong-Yin Zhu, Lun-Gen Lu
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 10 Issue 23 Pg. 3394-8 (Dec 01 2004) ISSN: 1007-9327 [Print] United States
• PMID: 15526354 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chromosomal Proteins, Non-Histone
• Cyclin-Dependent Kinase Inhibitor p16
• DNA-Binding Proteins
• MAS1 protein, human
• MECP2 protein, human
• Methyl-CpG-Binding Protein 2
• Proto-Oncogene Mas
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-myc
• RNA, Messenger
• Repressor Proteins
• DNA (Cytosine-5-)-Methyltransferase 1
• DNA (Cytosine-5-)-Methyltransferases
• DNMT1 protein, human
• MSH2 protein, human
• MutS Homolog 2 Protein

Topics

• Aged
• Chromosomal Proteins, Non-Histone (genetics)
• Cyclin-Dependent Kinase Inhibitor p16 (genetics)
• DNA (Cytosine-5-)-Methyltransferase 1
• DNA (Cytosine-5-)-Methyltransferases (genetics)
• DNA Methylation
• DNA-Binding Proteins (genetics)
• Female
• Gastric Mucosa (physiology)
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Methyl-CpG-Binding Protein 2
• Middle Aged
• MutS Homolog 2 Protein
• Promoter Regions, Genetic (physiology)
• Proto-Oncogene Mas
• Proto-Oncogene Proteins (genetics)
• Proto-Oncogene Proteins c-myc (genetics)
• RNA, Messenger (analysis)
• Repressor Proteins (genetics)
• Stomach Neoplasms (genetics, pathology, physiopathology)
• Transcription, Genetic