Gastrokine 1 inhibits gastrin-induced cell proliferation

Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
Olga KimWon Sang Park

Abstract

Gastrokine 1 (GKN1) acts as a gastric tumor suppressor. Here, we investigated whether GKN1 contributes to the maintenance of gastric mucosal homeostasis by regulating gastrin-induced gastric epithelial cell growth. We assessed the effects of gastrin and GKN1 on cell proliferation in stable AGS(GKN1) and MKN1(GKN1) gastric cancer cell lines and HFE-145 nonneoplastic epithelial cells. Cell viability and proliferation were analyzed by MTT and BrdU incorporation assays, respectively. Cell cycle and expression of growth factor receptors were examined by flow cytometry and Western blot analyses. Gastrin treatment stimulated a significant time-dependent increase in cell viability and proliferation in AGS(mock) and MKN1(mock), but not in HFE-145, AGS(GKN1), and MKN1(GKN1), cells, which stably expressed GKN1. Additionally, gastrin markedly increased the S-phase cell population, whereas GKN1 significantly inhibited the effect of gastrin by regulating the expression of G1/S cell-cycle regulators. Furthermore, gastrin induced activation of the NF-kB and β-catenin signaling pathways and increased the expression of CCKBR, EGFR, and c-Met in AGS and MKN1 cells. However, GKN1 completely suppressed these effects of gastrin via downregulation of...Continue Reading

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Citations

Sep 4, 2016·Biochemical and Biophysical Research Communications·Min YangQing Sun
Apr 29, 2018·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Jung Hwan YoonWon Sang Park
Dec 14, 2018·BMC Genomics·Amélie JuanchichAgnès Narcy
Jul 20, 2019·International Journal of Oncology·Judit Alarcón-MillánGloria Fernández-Tilapa

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