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- Title
IFN-β induces serine phosphorylation of Stat-1 in Ewing's sarcoma cells and mediates apoptosis via induction of IRF-1 and activation of caspase-7.
- Authors
Sancéau, Josiane; Hiscott, John; Delattre, Olivier; Wietzerbin, Juana
- Abstract
Four human cell lines derived from Ewing's sarcoma, EW-7, EW-1, COH and ORS, were investigated to establish the effects of human recombinant interferon-α2a and human recombinant interferon-β on cell proliferation and apoptosis. All four cell lines were much more sensitive to the antiproliferative effects of IFN-β than of IFN-α. Analysis of the early signals triggered by IFN-α and IFN-β demonstrated that the two IFNs were similarly effective in inducing tyrosine phosphorylation of the Jak-1 and Tyk-2 kinases and the transcription factors Stat-1 and Stat-2. Interestingly, an additional rapid phosphorylation of Stat-1 on serine was observed after IFN-β treatment, with concomitant activation of p38 mitogen-activated protein kinase. In these cells, Stat-1 Ser727 phosphorylation in response to IFN-β was found to be impaired by p38 MAPkinase inhibitor (SB203580). IFN-β induced the formation of the Interferon Stimulated Gene Factor 3 complex more efficiently than IFN-α, as well as sustained induction of IRF-1, which may account for its greater induction of 2′5′oligo(A)synthetase and greater inhibition of cell proliferation. IFN-β, but not IFN-α, induced apoptosis in wild-type p53 EW-7 and COH cell lines, but not in the mutated p53 EW-1 or ORS cell lines. The apoptosis induced by IFN-β in EW-7 and COH cell lines appeared to be mediated by IRF-1 and involved the activation of caspase-7. Ectopic expression of IRF-1 induced apoptosis in all four cell lines which correlated with the activation of caspase-7 and with the downregulation of the Bcl-2 oncoprotein, as observed for IFN-β-induced apoptosis in parental EW-7 and COH cell lines. Oncogene (2000) 19, 3372–3383
- Subjects
EWING'S sarcoma; PHOSPHORYLATION; APOPTOSIS; CELL lines; TRANSCRIPTION factors
- Publication
Oncogene, 2000, Vol 19, Issue 30, p3372
- ISSN
0950-9232
- Publication type
Article