title: TRAIL expression up-regulated by interferon-gamma via phosphorylation of STAT1 induces myeloma cell death.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hygiene, Division of Hematology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Miura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tsujioka
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Haruko
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: Megumi
authors.initials: M
authors.lastname: Maeda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Maolong
authors.initials: M
authors.lastname: Dong
authors.forename: Fuminori
authors.initials: F
authors.lastname: Hyodoh
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Yata
authors.forename: Hideho
authors.initials: H
authors.lastname: Wada
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugihara
authors.forename: Takemi
authors.initials: T
authors.lastname: Otsuki
mesh_terms: D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D017931:DNA Primers; D050794:STAT1 Transcription Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D007371:Interferon-gamma