TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000673742
  • Gene Name:CASP8 (caspase 8)
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:RT-PCR
  • mRNA Pathway:TRAIL induces apoptosis signaling pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:IFNalpha
  • Drug Method:up-regulated the gene expression

Disease basic infommation

  • Disease:hepatocellular carcinoma
  • Tissue:cell line (Huh7)

Other information

  • Title:Interferon-alpha enhances TRAIL-mediated apoptosis by up-regulating caspase-8 transcription in human hepatoma cells
  • Journal:J Hepatol
  • Published:2006
  • PubMed ID:16225956
  • Abstract:Background/aims:IFNalpha is an approved treatment option for patients chronically infected with the hepatitis B and C viruses. Additionally, there is an indication for tumor therapy. The exact mechanisms underlying the antiviral and antitumor effects of IFNalpha are not completely understood. In this study, we investigated if the pro-apoptotic factor caspase-8 is a target gene of IFNalpha signalling. Methods:Huh7 hepatoma cells were used for measuring caspase-8 promoter activity in luciferase reporter assays after IFNalpha stimulation. Caspase-8 expression was monitored by RT-PCR, immunoblotting and measurement of enzymatic activity. Functional caspase-8 promoter elements were identified in gelshift assays and by site directed mutagenesis. Caspase-8 was inhibited using siRNA. Results:IFNalpha treatment induced caspase-8 promoter activity and mRNA expression. We identified a unique promoter element mediating the IFNalpha-dependent increase in caspase-8 transcription. Up-regulation of caspase-8 expression by IFNalpha had no impact on the rate of apoptosis per se. However, co-stimulation with IFNalpha doubled TRAIL-mediated apoptosis and enzymatic caspase-8 activity. The synergistic effect of TRAIL and IFNalpha could be blocked by inhibiting caspase-8 expression. Conclusions:We demonstrate that caspase-8 is a target gene of IFNalpha and provide evidence showing that IFNalpha treatment sensitizes cells for apoptosis via enhanced caspase-8 transcription.
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