Up-regulation of WNT10A by tumor necrosis factor alpha and Helicobacter pylori in gastric cancer

Int J Oncol. 2001 Sep;19(3):533-6.


WNT signaling pathway is implicated in carcinogenesis and embryogenesis. We have previously cloned and characterized WNT10A and WNT6, which are clustered in human chromosome 2q35 region. In this study, we investigated expression of WNT10A and WNT6 in gastric cancer. The 3.0- and 2.4-kb WNT10A mRNAs were expressed in gastric cancer cell lines MKN7, MKN45 and MKN74. The 2.0-kb WNT6 mRNA was expressed in gastric cancer cell lines MKN28 and MKN74. WNT10A was up-regulated in 3 out of 6 cases of primary gastric cancer, while WNT6 was not up-regulated in primary gastric cancer. Effects of inflammatory cytokines and Helicobacter pylori (H. pylori) on expression of WNT10A and WNT6 were next investigated. Interferon gamma (IFNgamma) failed to induce up-regulation of WNT10A and WNT6. Tumor necrosis factor alpha (TNFalpha) induced up-regulation of WNT10A in MKN45 cells. Up-regulation of WNT10A reached maximum at 6 h after TNFalpha treatment. H. pylori also induced up-regulation of WNT10A in MKN45 cells. These results strongly suggest that up-regulation of WNT10A induced by TNFalpha and H. pylori might play key roles in human gastric cancer through activation of WNT--beta-catenin--TCF signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • DNA Primers / chemistry
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / microbiology*
  • Helicobacter pylori / physiology*
  • Humans
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / microbiology*
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / microbiology
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Up-Regulation
  • Wnt Proteins


  • DNA Primers
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • WNT10A protein, human
  • WNT6 protein, human
  • Wnt Proteins
  • Wnt10a protein, mouse