Fas-mediated apoptosis and expression of related genes in human malignant hematopoietic cells

Exp Mol Med. 2000 Dec 31;32(4):246-54. doi: 10.1038/emm.2000.41.


Fas transduces apoptotic signals upon cross-linking with the Fas ligand (FasL), which is experimentally replaced by agonistic anti-Fas monoclonal antibodies (mAb). Of eight human malignant hematopoietic cell lines (HL-60, KG-1, THP-1, K562, U937, Jurkat, IM-9, RPMI-8226) examined by flow cytometric analysis, all, except K562, were found to be positive for surface Fas antigen. However, despite surface Fas expression, the agonistic anti-Fas mAb (7C11) induced apoptosis in only three of seven Fas-expressing cell lines (KG-1, Jurkat and IM-9). This Fas-resistance did not correlated with high levels of mRNA either for DcR3, a decoy receptor for FasL, or for FAP-1, a Fas-associated phosphatase that can block the apoptotic function of Fas. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis did not show consistent differences in the expression of Bcl-2 and Bax between Fas-sensitive and Fas-resistant cell lines examined. These findings indicated that the presence or absence of mRNA expression of DcR3, FAP-1, Bcl-2 and Bax did not always correlate with relative sensitivity to Fas-mediated apoptosis. Treatment of cells with cycloheximide converted the phenotype of resistant cell lines from Fas-resistant to Fas-sensitive, and enhanced the sensitivity of Fas-sensitive cell lines. These results suggest that the Fas-resistance is dependent on the presence of labile proteins that determine resistance to Fas-mediated apoptosis and the apoptotic machinery is already in place in Fas-resistant cell lines.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics
  • Cycloheximide / pharmacology
  • Fas Ligand Protein
  • Gene Expression Regulation, Neoplastic
  • Hematologic Neoplasms / genetics*
  • Hematologic Neoplasms / metabolism
  • Humans
  • Membrane Glycoproteins / metabolism*
  • Protein Synthesis Inhibitors / pharmacology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 13
  • Protein Tyrosine Phosphatases / biosynthesis
  • Protein Tyrosine Phosphatases / genetics
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / genetics
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Member 6b
  • Signal Transduction
  • Tumor Cells, Cultured
  • bcl-2-Associated X Protein
  • fas Receptor / metabolism*


  • BAX protein, human
  • Carrier Proteins
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Protein Synthesis Inhibitors
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Cell Surface
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Member 6b
  • TNFRSF6B protein, human
  • bcl-2-Associated X Protein
  • fas Receptor
  • Cycloheximide
  • PTPN13 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 13
  • Protein Tyrosine Phosphatases