Esophageal Cancer
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 15, 2003; 9(6): 1174-1178
Published online Jun 15, 2003. doi: 10.3748/wjg.v9.i6.1174
Expression of ECRG4, a novel esophageal cancer-related gene, downregulated by CpG island hypermethylation in human esophageal squamous cell carcinoma
Chun-Mei Yue, Da-Jun Deng, Mei-Xia Bi, Li-Ping Guo, Shih-Hsin Lu
Chun-Mei Yue, Mei-Xia Bi, Li-Ping Guo, Shih-Hsin Lu, Department of Etiology and Carcinogenesis, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China
Da-Jun Deng, Beijing Institute for Cancer Research, School of Oncology, Peking University, Beijing, 100034, China
Author contributions: All authors contributed equally to the work.
Supported by grant from State Key Basic Program (G1998051204) and from the Ministry of Education, China
Correspondence to: Shih-Hsin Lu, Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences, Beijing 100021, China. shlu@public.bta.net.cn
Telephone: +86-10-67712368 Fax: +86-10-67712368
Received: March 2, 2003
Revised: March 4, 2003
Accepted: March 29, 2003
Published online: June 15, 2003
Abstract

AIM: To study the mechanisms responsible for inactivation of a novel esophageal cancer related gene 4 (ECRG4) in esophageal squamous cell carcinoma (ESCC).

METHODS: A pair of primers was designed to amplify a 220 bp fragment, which contains 16 CpG sites in the core promoter region of the ECRG 4 gene. PCR products of bisulfite-modified CpG islands were analyzed by denaturing high-performance liquid chromatography (DHPLC), which were confirmed by DNA sequencing. The methylation status of ECRG 4 promoter in 20 cases of esophageal cancer and the adjacent normal tissues, 5 human tumor cell lines (esophageal cancer cell line-NEC, EC109, EC9706; gastric cancer cell line- GLC; human embryo kidney cell line-Hek293) and 2 normal esophagus tissues were detected. The expression level of the ECRG 4 gene in these samples was examined by RT-PCR.

RESULTS: The expression level of ECRG 4 gene was varied. Of 20 esophageal cancer tissues, nine were unexpressed, six were lowly expressed and five were highly expressed compared with the adjacent tissues and the 2 normal esophageal epithelia. In addition, 4 out of the 5 human cell lines were also unexpressed. A high frequency of methylation was revealed in 12 (8 unexpressed and 4 lowly expressed) of the 15 (80%) downregulated cancer tissues and 3 of the 4 unexpressed cell lines. No methylation peak was observed in the two highly expressed normal esophageal epithelia and the methylation frequency was low (3/20) among the 20 cases in the highly expressed adjacent tissues. The methylation status of the samples was consistent with the result of DNA sequencing.

CONCLUSION: These results indicate that the inactivation of ECRG 4 gene by hypermethylation is a frequent molecular event in ESCC and may be involved in the carcinogenesis of this cancer.

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