Gastric Cancer
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 1, 2004; 10(23): 3394-3398
Published online Dec 1, 2004. doi: 10.3748/wjg.v10.i23.3394
Expression of Dnmt1, demethylase, MeCP2 and methylation of tumor-related genes in human gastric cancer
Jing-Yuan Fang, Zhong-Hua Cheng, Ying-Xuan Chen, Rong Lu, Li Yang, Hong-Yin Zhu, Lun-Gen Lu
Jing-Yuan Fang, Zhong-Hua Cheng, Ying-Xuan Chen, Rong Lu, Li Yang, Hong-Yin Zhu, Lun-Gen Lu, Shanghai Institute of Digestive Disease, Shanghai Second Medical University Renji Hospital, Shanghai 200001, China
Author contributions: All authors contributed equally to the work.
Supported by National Natural Science Foundation of China, No. 30170413; Foundation for the Author of National Excellent Doctoral Dissertation of China, No.199946 and the Key Project Funds of Shanghai Education Committee
Correspondence to: Dr. Jing-Yuan Fang, Shanghai Institute of Digestive Disease, 145 Shandong Zhong Road, Shanghai 200001, China.
Telephone: +86-21-63200874 Fax: +86-21-63266027
Received: March 27, 2004
Revised: April 3, 2004
Accepted: April 16, 2004
Published online: December 1, 2004

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, p16INK4A, hMSH2 and c-myc were detected by using real-time PCR or RT-PCR. Promoter methylation of p16INK4A, 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 p16INK4A 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.

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