Prolonged cell survival enhances peritoneal dissemination of gastric cancer cells

Oncogene. 1998 May;16(20):2681-6. doi: 10.1038/sj.onc.1201792.

Abstract

Bcl-2 and a Bcl-2-binding protein BAG-1 function in protection from apoptosis induced by a variety of stimuli. Deregulated expression of Bcl-2 leads to inhibition of apoptosis and is correlated with development of various cancers. Here, we provide evidence that prolonged cell survival introduced by overproduction of Bcl-2 or BAG-1 strongly enhances peritoneal dissemination of human gastric cancer MKN74 cells. Gene transfer-mediated overexpression of Bcl-2 or BAG-1 led to prolonged cell survival of MKN74 cells against serum-starved apoptosis and anoikis. When the viable transfectants were inoculated into the intraperitoneal cavity of BALB/c nude mice, the Bcl-2-expressing MKN74 cells and the BAG-1-expressing MKN74 cells exhibited strongly enhanced peritoneal dissemination in BALB/c nude mice and whole disseminated tumor weights were increased by 4-fold and 3.3-fold, respectively, compared with the control transfectants. The enhanced peritoneal dissemination of MKN74-Bcl-2 and MKN74-BAG-1 transfectants correlated well with resistance to cell death induced by serum-starvation and anoikis. However, the overexpression of Bcl-2 or BAG-1 caused no significant difference among the transfectants in cell growth rates, either in vitro or in vivo. Taken together, these studies demonstrate that resistance to apoptosis is a crucial factor for development of peritoneal dissemination of human gastric cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Apoptosis
  • Carrier Proteins / metabolism*
  • Cell Survival
  • DNA-Binding Proteins
  • Humans
  • Neoplasm Metastasis
  • Peritoneal Neoplasms / secondary*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Transcription Factors
  • Transfection
  • Tumor Cells, Cultured

Substances

  • BCL2-associated athanogene 1 protein
  • Carrier Proteins
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Transcription Factors