Expression of genes that regulate Fas signalling and Fas-mediated apoptosis in colon carcinoma cells

Cell Death Differ. 1998 May;5(5):450-7. doi: 10.1038/sj.cdd.4400369.

Abstract

The expression of genes that regulate Fas-induced apoptosis has been examined in 10 human cultured colon carcinoma cell lines with defined and varied sensitivity to the cytolytic anti-Fas MoAb CH-11. Four lines demonstrated sensitivity to CH-11 (HT29, GC3/c1, TS-, Thy4), and six were resistant to the induction of apoptosis vis Fas. In nine lines expressing Fas, PCR-sequencing indicated that the death domain contained wt sequences. Downstream of Fas, expression of FADD/MORT1 and FLICE, essential components of the DISC, and negative regulators of Fas signalling including sFas, FAP-1 and Bcl-2, showed no correlation between levels of expression and sensitivity to Fas-mediated cytotoxicity. However, levels of the Fas antigen varied by >1000-fold, and correlated with CH-11 sensitivity. Following fourfold elevation in Fas expression in HT29 cells treated with interferon-gamma, a synergistic effect on Fas-mediated apoptosis was obtained when CH-11 and interferon-gamma were combined.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Antibodies, Monoclonal / immunology
  • Apoptosis / genetics*
  • Carrier Proteins / genetics
  • Caspase 8
  • Caspase 9
  • Caspases / genetics
  • Cell Division / genetics
  • Cell Survival / genetics
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / immunology
  • Fas-Associated Death Domain Protein
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interferon-gamma / pharmacology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 13
  • Protein Tyrosine Phosphatases / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Messenger / genetics
  • Signal Transduction / genetics*
  • Tumor Cells, Cultured
  • fas Receptor / genetics*
  • fas Receptor / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • Antibodies, Monoclonal
  • Carrier Proteins
  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • fas Receptor
  • Interferon-gamma
  • PTPN13 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 13
  • Protein Tyrosine Phosphatases
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 8
  • Caspase 9
  • Caspases