CagA promotes proliferation and inhibits apoptosis of GES-1 cells by upregulating TRAF1/4-1BB

Mol Med Rep. 2017 Aug;16(2):1262-1268. doi: 10.3892/mmr.2017.6757. Epub 2017 Jun 12.

Abstract

Cytotoxin-associated gene A (CagA) is one of the most important virulence factors of Helicobacter pylori, and serves a role in H. pylori‑mediated tumorigenesis in gastric cancer. However, the underlying molecular mechanism remains to be elucidated. The present study aimed to investigate the effects of CagA on the proliferation and apoptosis of GES‑1 cells, and the underlying mechanism. A CagA eukaryotic expression plasmid was constructed and transfected into GES‑1 cells. The mRNA and protein levels of CagA, tumor necrosis factor receptor‑associated factor 1 (TRAF1) and tumor necrosis factor receptor superfamily member 9 (4‑1BB) were determined using the reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. Western blot and ELISA analysis was used to detect the release of interleukin (IL)‑8. An MTT assay and flow cytometric analysis was used to assess cell viability and apoptosis, respectively. Ectopic expression of CagA markedly increased TRAF1 and 4‑1BB mRNA and protein levels in GES‑1 cells. CagA increased the expression and release of IL‑8 in GES‑1 cells. The expression of CagA significantly promoted the proliferation (P<0.05) and inhibited the apoptosis (P<0.05) of GES‑1 cells. In conclusion, CagA upregulated TRAF1/4‑1BB, thereby promoting the proliferation and inhibiting the apoptosis of GES-1 cells.

MeSH terms

  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / metabolism*
  • Apoptosis
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cell Line
  • Cell Proliferation
  • Ectopic Gene Expression
  • Gene Expression Regulation
  • Helicobacter Infections
  • Helicobacter pylori
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • TNF Receptor-Associated Factor 1 / genetics*
  • TNF Receptor-Associated Factor 1 / metabolism
  • Transfection
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / genetics*
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / metabolism

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Interleukin-8
  • TNF Receptor-Associated Factor 1
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • cagA protein, Helicobacter pylori