Methylation of TIMP3 in esophageal squamous cell carcinoma

doi:10.3748/wjg.14.203

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Esophageal Cancer

World J Gastroenterol. Jan 14, 2008; 14(2): 203-210
Published online Jan 14, 2008. doi: 10.3748/wjg.14.203

Methylation of TIMP3 in esophageal squamous cell carcinoma

Eric Smith, Neville J De Young, Zi-Qiang Tian, Maria Caruso, Andrew R Ruszkiewicz, Jun-Feng Liu, Glyn G Jamieson, Paul A Drew

Eric Smith, Neville J De Young, Glyn G Jamieson, Discipline of Surgery, School of Medicine, Faculty of Health Sciences, The University of Adelaide, Royal Adelaide Hospital, South Australia 5005, Australia

Zi-Qiang Tian, Jun-Feng Liu, Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China

Maria Caruso, Andrew R Ruszkiewicz, Division of Tissue Pathology, Institute of Medical and Veterinary Science, Adelaide, South Australia 5000, Australia

Paul A Drew, School of Nursing and Midwifery, Flinders University, Bedford Park, South Australia 5042, Australia

Correspondence to: Eric Smith, Discipline of Surgery, School of Medicine, Faculty of Health Sciences, The University of Adelaide, Royal Adelaide Hospital, South Australia 5005, Australia. eric.smith@adelaide.edu.au

Telephone: +61-8-82222855

Fax: +61-8-82225896

Received: June 4, 2007
Revised: July 29, 2007
Published online: January 14, 2008

Abstract

AIM: To measure the frequency of DNA methylation of the tissue inhibitor of metalloproteinase 3 (TIMP3) promoter and relate this to any change of gene expression in esophageal squamous cell carcinoma in patients from a region of high incidence in China.

METHODS: Cancer cell lines were treated with or without the demethylating reagent 5-aza-2’-deoxycytidine. Methylation of the TIMP3 promoter was assessed in three regions by melt curve analysis and its expression was assessed by real-time RT-PCR. Tumors and proximal resection margins were obtained from 64 patients with esophageal squamous cell carcinoma from a region of high incidence in China. Methylation was assessed by melt curve analysis and expression by immunohistochemistry.

RESULTS: Methylation in one of the three promoter regions assessed correlated with gene silencing in esophageal cell lines. A degree of methylation of TIMP3 was found in only four esophageal squamous cell carcinomas, and partial loss of TIMP3 protein expression in just one.

CONCLUSION: Methylation and loss of expression of TIMP3 occurs infrequently in esophageal squamous cell carcinoma in a region of high incidence in China.

Keywords: Esophageal squamous cell carcinoma; Immunohistochemistry; Methylation; Tissue inhibitor of metalloproteinase 3