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http://dx.doi.org/10.5230/jgc.2013.13.4.232

Gastrokine 1 Expression in the Human Gastric Mucosa Is Closely Associated with the Degree of Gastritis and DNA Methylation  

Choi, Won Suk (Department of Pathology, The Catholic University of Korea, School of Medicine)
Seo, Ho Suk (Department of General Surgery, The Catholic University of Korea, School of Medicine)
Song, Kyo Young (Department of General Surgery, The Catholic University of Korea, School of Medicine)
Yoon, Jung Hwan (Department of Pathology, The Catholic University of Korea, School of Medicine)
Kim, Olga (Department of Pathology, The Catholic University of Korea, School of Medicine)
Nam, Suk Woo (Department of Pathology, The Catholic University of Korea, School of Medicine)
Lee, Jung Yong (Department of Pathology, The Catholic University of Korea, School of Medicine)
Park, Won Sang (Department of Pathology, The Catholic University of Korea, School of Medicine)
Publication Information
Journal of Gastric Cancer / v.13, no.4, 2013 , pp. 232-241 More about this Journal
Abstract
Purpose: Gastrokine 1 plays an important role in gastric mucosal defense. Additionally, the Gastrokine 1-miR-185-DNMT1 axis has been shown to suppress gastric carcinogenesis through regulation of epigenetic alteration. Here, we investigated the effects of Gastrokine 1 on DNA methylation and gastritis. Materials and Methods: Expression of Gastrokine 1, DNMT1, EZH2, and c-Myc proteins, and the presence of Helicobacter pylori CagA protein were determined in 55 non-neoplastic gastric mucosal tissue samples by western blot analysis. The CpG island methylation phenotype was also examined using six markers (p16, hMLH1, CDH1, MINT1, MINT2 and MINT31) by methylation-specific polymerase chain reaction. Histological gastritis was assessed according to the updated Sydney classification system. Results: Reduced Gastrokine 1 expression was found in 20 of the 55 (36.4%) gastric mucosal tissue samples and was closely associated with miR-185 expression. The Gastrokine 1 expression level was inversely correlated with that of DNMT1, EZH2, and c-Myc, and closely associated with the degree of gastritis. The H. pylori CagA protein was detected in 26 of the 55 (47.3%) gastric mucosal tissues and was positively associated with the expression of DNMT1, EZH2, and c-Myc. In addition, 30 (54.5%) and 23 (41.9%) of the gastric mucosal tissues could be classified as CpG island methylation phenotype-low and CpG island methylation phenotype-high, respectively. Reduced expression of Gastrokine 1 and miR-185, and increased expression of DNMT1, EZH2, and c-Myc were detected in the CpG island methylation phenotype-high gastric mucosa. Conclusions: Gastrokine 1 has a crucial role in gastric inflammation and DNA methylation in gastric mucosa.
Keywords
Gastrokine 1; DNA methylation; microRNA-185; CagA protein; Gastric mucosa;
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