title: Gastrokine 1 regulates NF-κB signaling pathway and cytokine expression in gastric cancers.
abstract: Gastrokine 1 (GKN1) plays an important role in the gastric mucosal defense mechanism and also acts as a functional gastric tumor suppressor. In this study, we examined the effect of GKN1 on the expression of inflammatory mediators, including NF-κB, COX-2, and cytokines in GKN1-transfected AGS cells and shGKN1-transfected HFE-145 cells. Lymphocyte migration and cell viability were also analyzed after treatment with GKN1 and inflammatory cytokines in AGS cells by transwell chemotaxis and an MTT assay, respectively. In GKN1-transfected AGS cells, we observed inactivation and reduced expression of NF-κB and COX-2, whereas shGKN1-transfected HFE-145 cells showed activation and increased expression of NF-κB and COX-2. GKN1 expression induced production of inflammatory cytokines including IL-8 and -17A, but decreased expression of IL-6 and -10. We also found IL-17A expression in 9 (13.6%) out of 166 gastric cancer tissues and its expression was closely associated with GKN1 expression. GKN1 also acted as a chemoattractant for the migration of Jurkat T cells and peripheral B lymphocytes in the transwell assay. In addition, GKN1 significantly reduced cell viability in both AGS and HFE-145 cells. These data suggest that the GKN1 gene may inhibit progression of gastric epithelial cells to cancer cells by regulating NF-κB signaling pathway and cytokine expression.
authors: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea.
authors: Jung Hwan
authors: JH
authors: Yoon
authors: Mi La
authors: ML
authors: Cho
authors: Yoo Jin
authors: YJ
authors: Choi
authors: Ji Yeon
authors: JY
authors: Back
authors: Mi Kyung
authors: MK
authors: Park
authors: Suk Woo
authors: SW
authors: Lee
authors: Byung Joon
authors: BJ
authors: Choi
authors: Hassan
authors: H
authors: Ashktorab
authors: Duane T
authors: DT
authors: Smoot
authors: Suk Woo
authors: SW
authors: Nam
authors: Jung Young
authors: JY
authors: Lee
authors: Won Sang
authors: WS
authors: Park
mesh_terms: D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D036361:Peptide Hormones / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D016207:Cytokines; C477000:GKN1 protein, human; D016328:NF-kappa B; D009363:Neoplasm Proteins; D036361:Peptide Hormones; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human