Helicobacter pylori induces malignant transformation of gastric epithelial cells in vitro
Abstract:Yu X-W, Xu Y, Gong Y-H, Qian X, Yuan Y. Helicobacter pylori induces malignant transformation of gastric epithelial cells in vitro. APMIS 2011; 119: 187–197.
Epidemiologic studies have demonstrated that Helicobacter pylori infection is associated with increased risk for the development of gastric cancer. Animal studies have also shown that H. pylori infection leads to gastric carcinogenesis, especially intestinal phenotypes. However, no in vitro study has been carried out for cell transformation induced by H. pylori. The present study aimed to investigate whether ‘chronic’H. pylori infection induces gastric epithelial cell transformation, and elucidate the underlying mechanisms of transformation induced by H. pylori. The immortalized ‘normal’ gastric epithelial cell line, GES-1, was co-cultured for 45 days with H. pylori strains B975 and L301. The cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Ki-67 antigen, and colony formation assay. The cell transformation was determined by observing cell morphology and measuring the expression of E-cadherin, β-catenin, and transcription factor-4 (TCF-4) at both protein and mRNA levels. H. pylori induced morphologic changes in GES-1 cells and significantly increased the proliferation of GES-1 cells. Moreover, H. pylori up-regulated the expression of β-catenin and TCF-4, and also induced the nuclear accumulation of β-catenin. In addition, the diffusive gastric cancer-related gene, E-cadherin, was up-regulated at the protein level, but down-regulated at the mRNA level. H. pylori infection is capable of inducing GES-1 transformation to present with the characteristics of intestinal-type gastric cancers in vitro, likely through the β-catenin/TCF-4 signaling pathway.
Document Type: Research Article
Affiliations: Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University; the key Cancer Control Laboratory in Liaoning Province, Shenyang
Publication date: March 1, 2011