TRAIL expression up-regulated by interferon-gamma via phosphorylation of STAT1 induces myeloma cell death.
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.
Miura
Yoshie
Y
Department of Hygiene, Division of Hematology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
Tsujioka
Takayuki
T
Nishimura
Yasumitsu
Y
Sakaguchi
Haruko
H
Maeda
Megumi
M
Hayashi
Hiroaki
H
Dong
Maolong
M
Hyodoh
Fuminori
F
Yata
Ken-Ichiro
K
Wada
Hideho
H
Sugihara
Takashi
T
Otsuki
Takemi
T
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*
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