Activator protein-1 involved in growth inhibition by RASSF1A gene in the human gastric carcinoma cell line SGC7901

World J Gastroenterol. 2008 Mar 7;14(9):1437-43. doi: 10.3748/wjg.14.1437.

Abstract

Aim: To investigate the role of Ras association domain family protein 1 isoform A (RASSF1A) in gastric tumorigenesis.

Methods: Through over-expression of RASSF1A gene in the SGC7901 cell line which was induced by a lipofectamine-mediated gene transfer approach. Activator protein-1 (AP-1) DNA binding activity was measured by electrophoretic mobility shift assay (EMSA).

Results: Compared with the control clones, cells over-expressing RASSF1A exhibited significant inhibition of cell growth with G1 cell cycle arrest in vitro and in vivo. The over-expression of RASSF1A significantly inhibited AP-1 activity in SGC7901 cells (0.981+/-0.011 vs 0.354+/-0.053, P<0.001). In addition, both Western blot analysis and immunocytochemistry demonstrated that RASSF1A down-regulated the expression of c-Fos (0.975+/-0.02 vs 0.095+/-0.024, P<0.001) but not c-Jun.

Conclusion: Over-expression of RASSF1A inhibits the growth of SGC7901 cells by negatively regulating the AP-1 activity, the latter in turn negatively signals cell proliferation.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology*
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Proto-Oncogene Proteins c-fos
  • RASSF1 protein, human
  • Transcription Factor AP-1
  • Tumor Suppressor Proteins