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

Yoshie Miura1, Takayuki Tsujioka, Yasumitsu Nishimura

  • 1Department of Hygiene, Division of Hematology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.

Anticancer Research
|January 5, 2007
PubMed
Abstract

Insights

Interferon-gamma (IFN-gamma) inhibits myeloma cell growth by activating the JAK/STAT pathway, increasing TRAIL production, and inducing apoptosis. This suggests IFN-gamma

Area of Science:

  • Immunology
  • Molecular Biology
  • Oncology

Background:

  • Interferon-alpha (IFN-alpha) effects are well-studied.
  • Interferon-gamma (IFN-gamma) biological effects are less understood.

Purpose of the Study:

  • Investigate IFN-gamma's effects on human myeloma cell lines.
  • Characterize the molecular mechanisms of IFN-gamma-induced growth inhibition.

Main Methods:

  • Cultured eleven human myeloma cell lines with IFN-gamma.
  • Analyzed TRAIL expression and JAK/STAT pathway in KMS-20 cells.

Main Results:

  • IFN-gamma induced growth inhibition in KMS-20 cells.
  • Observed up-regulation of TRAIL and STAT1 activation.
  • IFN-gamma triggered TRAIL hyperproduction.

Conclusions:

  • IFN-gamma activates the JAK/STAT pathway, specifically STAT1 phosphorylation.
  • Enhanced TRAIL secretion and its auto/paracrine use induce apoptosis.
  • IFN-gamma shows potential for future myeloma combination therapies.

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