Gastrokine 1 Expression in the Human Gastric Mucosa Is Closely Associated with the Degree of Gastritis and DNA Methylation.
10.5230/jgc.2013.13.4.232
- Author:
Won Suk CHOI
1
;
Ho Suk SEO
;
Kyo Young SONG
;
Jung Hwan YOON
;
Olga KIM
;
Suk Woo NAM
;
Jung Yong LEE
;
Won Sang PARK
Author Information
1. Department of Pathology, The Catholic University of Korea, School of Medicine, Seoul, Korea. wonsang@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
Gastrokine 1;
DNA methylation;
microRNA-185;
CagA protein;
Gastric mucosa
- MeSH:
Axis, Cervical Vertebra;
Blotting, Western;
Carcinogenesis;
Classification;
CpG Islands;
DNA Methylation*;
DNA*;
Epigenomics;
Gastric Mucosa*;
Gastritis*;
Helicobacter pylori;
Humans*;
Inflammation;
Methylation;
Mucous Membrane;
Phenotype;
Polymerase Chain Reaction;
Proto-Oncogene Proteins c-myc
- From:Journal of Gastric Cancer
2013;13(4):232-241
- CountryRepublic of Korea
- Language:English
-
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.
