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Vol. 71, No. 3, 2004
Issue release date: April 2004
Section title: Original Paper
Pathobiology 2004;71:137–143
(DOI:10.1159/000076468)

Frequent Loss of RUNX3 Expression by Promoter Hypermethylation in Gastric Carcinoma

Oshimo Y. · Oue N. · Mitani Y. · Nakayama H. · Kitadai Y. · Yoshida K. · Ito Y. · Chayama K. · Yasui W.
Departments of aMolecular Pathology, bMedicine and Molecular Science, Hiroshima University Graduate School of Biomedical Sciences, and cSurgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan; dInstitute of Molecular and Cell Biology, National University of Singapore, Singapore, Singapore

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 5/29/2003
Accepted: 7/8/2003
Published online: 4/2/2004

Number of Print Pages: 7
Number of Figures: 3
Number of Tables: 1

ISSN: 1015-2008 (Print)
eISSN: 1423-0291 (Online)

For additional information: http://www.karger.com/PAT

Abstract

The RUNX3 gene is a member of the Runt domain family of transcription factors that are master regulators of gene expression in major developmental pathways. Recently, lack of RUNX3 function was found to be associated with genesis and progression of gastric carcinoma. We studied methylation of CpG islands in the RUNX3 gene by methylation-specific PCR in 80 gastric carcinoma specimens, 45 corresponding non-neoplastic mucosae, and 7 gastric carcinoma cell lines. We also measured levels of RUNX3 mRNA in 50 of the gastric carcinoma cases by quantitative RT-PCR and in the gastric carcinoma cell lines by RT-PCR. Hypermethylation of the RUNX3 promoter was found in 57 (71%) of 80 gastric carcinomas, and promoter hypermethylation of RUNX3 occurred more frequently in intestinal and diffuse-adherent type tumors than in diffuse-scattered type tumors (p = 0.046). Reduced RUNX3 expression was associated with promoter hypermethylation (p = 0. 036), however, there was no correlation between RUNX3 mRNA expression levels and T grade, N grade, tumor stage, or histological type. In corresponding non-neoplastic mucosae, hypermethylation of the RUNX3 promoter was found in 38 (84%) of 45 specimens. Among seven gastric carcinoma cell lines, three cell lines (MKN-28, MKN-74, TMK-1) with diminished expression of RUNX3 had promoter methylation and three cell lines (MKN-1, MKN-7, MKN-45) with RUNX3 expression showed no promoter methylation. Our results overall suggest that transcriptional inactivation of RUNX3 by promoter hypermethylation may participate in the stomach carcinogenesis.


  

Author Contacts

Yasui Wataru
Department of Molecular Pathology
Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku
Hiroshima, 734-8551 (Japan)
Tel. +81 82 257 5145, Fax +81 82 257 5149, E-Mail wyasui@hiroshima-u.ac.jp

  

Article Information

Received: May 29, 2003
Accepted: July 8, 2003
Number of Print Pages : 7
Number of Figures : 3, Number of Tables : 1, Number of References : 34

  

Publication Details

Pathobiology
Founded 1938 as ‘Schweizerische Zeitschrift für allgemeine Pathologie und Bakteriologie’ by A. v. Albertini, A. Grumbach and H. Mooser

Vol. 71, No. 3, Year 2004 (Cover Date: Released April 2004)

Journal Editor: Ch. Wittekind, Leipzig
ISSN: 1015–2008 (print), 1423–0291 (Online)

For additional information:http://www.karger.com/pat


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 5/29/2003
Accepted: 7/8/2003
Published online: 4/2/2004

Number of Print Pages: 7
Number of Figures: 3
Number of Tables: 1

ISSN: 1015-2008 (Print)
eISSN: 1423-0291 (Online)

For additional information: http://www.karger.com/PAT


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