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Blood, Vol. 92 No. 8 (October 15), 1998:
pp. 2914-2923
Fas/APO-1 (CD95)-Mediated Apoptosis Is Activated by
Interferon- and Interferon- in Interleukin-6
(IL-6)-Dependent and IL-6-Independent Multiple Myeloma Cell Lines
Helena Spets,
Patrik Georgii-Hemming,
Jan Siljason,
Kenneth Nilsson, and
Helena Jernberg-Wiklund
From the Department of Genetics and Pathology, Unit of Pathology,
University Hospital, Uppsala, Sweden.
A poor response to Fas-induced apoptosis is evident in some multiple
myeloma (MM) cell lines and primary cells. In this study, we have
examined the possibility to increase the sensitivity to Fas-induced
apoptosis by pretreatment of MM cells with interferon- (IFN-) or
interferon- (IFN-). Both IFN- and IFN- markedly increased
the Fas-induced apoptosis in all cell lines tested (U-266-1970, U-266-1984, and U-1958). In the U-266-1970 and U-1958 cell lines, pretreatment with either IFN- or IFN- also inhibited
proliferation in a dose-dependent manner. In contrast, IFN-
activation of the Fas death pathway in the U-266-1984 cells was not
accompanied by growth inhibition. Incubation with the IFNs increased
the Fas antigen expression in one of three cell lines but did not alter the expression of Bcl-2 or Bax. The IFNs are important regulators of
growth and survival in MM cells. Our results suggest that activation of
Fas-mediated apoptosis is a novel mechanism by which the IFNs exert
inhibitory effects on MM cells.
© 1998 by The American Society of Hematology.
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