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

Jung Hwan Yoon, Mi La Cho, Yoo Jin Choi, Ji Yeon Back, Mi Kyung Park, Suk Woo Lee, Byung Joon Choi, Hassan Ashktorab, Duane T. Smoot, Suk Woo Nam, Jung Young Lee, Won Sang Park

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1800-1809
Number of pages10
JournalJournal of cellular biochemistry
Volume114
Issue number8
DOIs
StatePublished - Aug 1 2013

Keywords

  • CYTOKINE
  • GASTRIC CANCER
  • GKN1
  • INFLAMMATORY MEDIATOR
  • NF-κB

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Yoon, J. H., La Cho, M., Choi, Y. J., Back, J. Y., Park, M. K., Lee, S. W., Choi, B. J., Ashktorab, H., Smoot, D. T., Nam, S. W., Lee, J. Y., & Park, W. S. (2013). Gastrokine 1 regulates NF-κB signaling pathway and cytokine expression in gastric cancers. Journal of cellular biochemistry, 114(8), 1800-1809. https://doi.org/10.1002/jcb.24524