TRAIL expression up-regulated by interferon-gamma via phosphorylation of STAT1 induces myeloma cell death

Anticancer Res. 2006 Nov-Dec;26(6B):4115-24.

Abstract

Background: Although the cellular and molecular biological effects of interferon (IFN)-alpha have been well-investigated, the effects of IFN-gamma are less understood.

Materials and methods: Eleven human myeloma cell lines with various myeloma-specific chromosomal translocations and overexpression of oncogenes were cultured with 1000 U/ml of IFN-gamma. In the KMS-20 cells, which showed growth inhibition due to IFN-gamma, trail expression, status of the Janus kinase (JAK)/STAT pathway were analyzed.

Results: KMS-20 cells showed marked up-regulation of trail, activation of STAT1 and TRAIL hyperproduction induced by IFN-gamma.

Conclusion: The effects of IFN-gamma on growth inhibition of KMS-20 cells were characterized by activation of the JAK/STAT signalling pathway, particularly STAT1 phosphorylation, enhanced secretion of TRAIL, and auto/paracrine usage of secreted TRAIL to induce apoptotic cell death. From these results, IFN-gamma may be considered one of the drugs to be used in future multidrug chemotherapeutic regimens for myeloma patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Division / drug effects
  • Cell Line, Tumor
  • DNA Primers
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Interferon-gamma / pharmacology*
  • Multiple Myeloma / metabolism*
  • Multiple Myeloma / pathology
  • Phosphorylation
  • STAT1 Transcription Factor / metabolism*
  • TNF-Related Apoptosis-Inducing Ligand / genetics
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*
  • Tyrphostins / pharmacology
  • Up-Regulation / physiology*

Substances

  • DNA Primers
  • STAT1 Transcription Factor
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tyrphostins
  • alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
  • Interferon-gamma