Gastrokine 1 regulates NF-κB signaling pathway and cytokine expression in gastric cancers†‡
Jung Hwan Yoon
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Search for more papers by this authorMi La Cho
Rheumatism Research Center, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Search for more papers by this authorYoo Jin Choi
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Search for more papers by this authorJi Yeon Back
Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
Search for more papers by this authorMi Kyung Park
Rheumatism Research Center, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Search for more papers by this authorSuk Woo Lee
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Search for more papers by this authorByung Joon Choi
Department of Pediatrics, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Search for more papers by this authorHassan Ashktorab
Department of Medicine, Howard University, Washington, District of Columbia 20060
Search for more papers by this authorDuane T. Smoot
Department of Medicine, Howard University, Washington, District of Columbia 20060
Search for more papers by this authorSuk Woo Nam
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Search for more papers by this authorJung Young Lee
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Search for more papers by this authorCorresponding Author
Won Sang Park
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea.Search for more papers by this authorJung Hwan Yoon
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Search for more papers by this authorMi La Cho
Rheumatism Research Center, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Search for more papers by this authorYoo Jin Choi
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Search for more papers by this authorJi Yeon Back
Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
Search for more papers by this authorMi Kyung Park
Rheumatism Research Center, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Search for more papers by this authorSuk Woo Lee
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Search for more papers by this authorByung Joon Choi
Department of Pediatrics, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Search for more papers by this authorHassan Ashktorab
Department of Medicine, Howard University, Washington, District of Columbia 20060
Search for more papers by this authorDuane T. Smoot
Department of Medicine, Howard University, Washington, District of Columbia 20060
Search for more papers by this authorSuk Woo Nam
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Search for more papers by this authorJung Young Lee
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Search for more papers by this authorCorresponding Author
Won Sang Park
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea.Search for more papers by this authorThe authors declare that they have no conflicts of interest.
Author contributions: J.H.Y., M.L.C., and W.S.P. conceived and designed the experiments, J.H.Y., M.L.C., Y.J.C., J.Y.B., M.K.P., S.W.L., B.J.C., H.A., and D.T.S. performed the experiments, J.H.Y. and W.S.P. analyzed the data, H.A., D.T.S., S.W.N., and J.Y.L. contributed reagents/materials/analysis tools, and W.S.P. and M.L.C. wrote the paper.
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. J. Cell. Biochem. 114: 1800–1809, 2013. © 2013 Wiley Periodicals, Inc.
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