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

Yoshie Miura, Takayuki Tsujioka, Yasumitsu Nishimura, Haruko Sakaguchi, Megumi Maeda, Hiroaki Hayashi, Maolong Dong, Fuminori Hyodoh, Ken Ichiro Yata, Hideho Wada, Takashi Sugihara, Takemi Otsuki

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23 Citations (Scopus)

Abstract

Background: Although the cellular and molecular biological effects of interferon (IFN)-α have been well-investigated, the effects of IFN-γ are less understood. Materials and Methods: Eleven human myeloma cell lines with various myeloma-specific chromosomal translocations and overexpression of oncogenes were cultured with 1,000 U/ml of IFN-γ. In the KMS-20 cells, which showed growth inhibition due to IFN-γ, 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-γ. Conclusion: The effects of IFN-γ 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-γ may be considered one of the drugs to be used in future multidrug chemotherapeutic regimens for myeloma patients.

Original languageEnglish
Pages (from-to)4115-4124
Number of pages10
JournalAnticancer research
Volume26
Issue number6 B
Publication statusPublished - Nov 1 2006
Externally publishedYes

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Keywords

  • IFN-γ
  • Myeloma
  • STAT1
  • TRAIL

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Miura, Y., Tsujioka, T., Nishimura, Y., Sakaguchi, H., Maeda, M., Hayashi, H., Dong, M., Hyodoh, F., Yata, K. I., Wada, H., Sugihara, T., & Otsuki, T. (2006). TRAIL expression up-regulated by interferon-γ via phosphorylation of STAT1 induces myeloma cell death. Anticancer research, 26(6 B), 4115-4124.