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  • Title: TRAIL expression up-regulated by interferon-gamma via phosphorylation of STAT1 induces myeloma cell death.
    Author: Miura Y, Tsujioka T, Nishimura Y, Sakaguchi H, Maeda M, Hayashi H, Dong M, Hyodoh F, Yata K, Wada H, Sugihara T, Otsuki T.
    Journal: Anticancer Res; 2006; 26(6B):4115-24. PubMed ID: 17201122.
    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.
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