Tumor suppressor ING4 overexpression contributes to proliferation and invasion inhibition in gastric carcinoma by suppressing the NF-κB signaling pathway

Mol Biol Rep. 2013 Oct;40(10):5723-32. doi: 10.1007/s11033-013-2675-3. Epub 2013 Sep 22.

Abstract

There is growing evidence that inhibitor of growth 4 (ING4) plays a pivotal role in development and progression of multiple different tumors; however, its precise function in gastric carcinoma remains to be elucidated. In the present study, we investigated ING4 level in gastric carcinoma tissues and cells, and preliminarily elucidated the role of ING4 in the proliferation and invasion of gastric carcinoma. The results demonstrated that expressions of ING4 mRNA and protein in gastric carcinoma tissues and cells were significantly lower than those in normal tissues and cells (P < 0.05). ING4 level in gastric carcinoma cells stably expressing ING4 was markedly higher than those in untreated group and empty vector pcDNA3.1 group (P < 0.05). Elevated ING4 level resulted in the inhibition of proliferation and invasion in three of gastric carcinoma cell lines MKN-28, SGC-7901 and MKN-45. Most notably, increased ING4 level evidently evoked the down-regulation of p65, p-IκBα, MMP-9 and uPA proteins and the up-regulation of IκBα protein. Our results presented herein suggest that ING4 level elevation mediated proliferation and invasion inhibition may be tightly associated with the suppression of NF-κB signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • NF-kappa B / metabolism*
  • Neoplasm Invasiveness
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction* / genetics
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology*
  • Transfection
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • Homeodomain Proteins
  • ING4 protein, human
  • NF-kappa B
  • RNA, Messenger
  • Tumor Suppressor Proteins