title: Inactivation of the Gastrokine 1 gene in gastric adenomas and carcinomas.
abstract: Gastrokine 1 (GKN1) plays a role in the gastric mucosal defence mechanism and may be a gastric tumour suppressor. We have investigated whether inactivation of the GKN1 gene is involved in the development and/or progression of gastric cancers. GKN1 protein expression was examined in gastric adenomas and cancer and we also analysed GKN1 mutation and epigenetic alteration, DNA copy number change and mRNA transcript expression. The effect of GKN1 on cell proliferation and death was examined in wild-type GKN1-transfected AGS gastric cancer cells. Reduced or loss of GKN1 expression was detected in 36 (90%) and 170 (89.5%) of 40 adenomas and 190 gastric cancers, respectively. Statistically, there was no significant relationship between altered expression of GKN1 protein and clinicopathological parameters, including depth of invasion, location and lymph node metastasis (χ(2) test, p > 0.05). In western blot analysis, absence or reduced expression was found in 21 (84.0%) of 25 gastric carcinomas. No mutation was detected in gastric tumours, and hypermethylation of GKN1 gene was found in two tumours. DNA copy number and mRNA transcript of GKN1 were significantly decreased in gastric cancers. In functional analysis, AGS gastric cancer cells transfected with GKN1 wild-type showed marked inhibition of cell proliferation and induction of cell death. These data suggest that inactivation of the GKN1 gene may play an important role in the development of sporadic gastric cancers, as an early event.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, Korea.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Yoon
authors.forename: Jae Hwi
authors.initials: JH
authors.lastname: Song
authors.forename: Cao
authors.initials: C
authors.lastname: Zhang
authors.forename: Meishan
authors.initials: M
authors.lastname: Jin
authors.forename: Young Hwi
authors.initials: YH
authors.lastname: Kang
authors.forename: Suk Woo
authors.initials: SW
authors.lastname: Nam
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Park
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D036361:Peptide Hormones / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; C477000:GKN1 protein, human; D009363:Neoplasm Proteins; D036361:Peptide Hormones; D012333:RNA, Messenger; D012334:RNA, Neoplasm