Gastrokine 1 regulates NF-κB signaling pathway and cytokine expression in gastric cancers.

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.