Cytokines Prevent Dexamethasone-induced Apoptosis via the Activation of Mitogen-activated Protein Kinase and Phosphatidylinositol 3-Kinase Pathways in a New Multiple Myeloma Cell Line
2000
A new human myeloma cell line, OPM-6, was established from the
peripheral blood of a patient with advanced IgG-κ plasma cell
leukemia. Cytogenetic and phenotypic analysis confirmed that the cells
were derived from the patient’s leukemic cells. Insulin-like growth
factor-1 (IGF-1) acts as an autocrine growth factor in these cells. In
addition, OPM-6 cells were particularly sensitive to dexamethasone
(DEX), when endogenous IGF-1 was blocked. Under these conditions,>
95% of the DEX-treated cells died within 36 h. Therefore, OPM-6
represents a potentially powerful tool for the analysis of the
molecular mechanisms of DEX-induced apoptosis, because it is possible
to easily analyze the direct effects of DEX using this system. Using
this culture system of OPM-6, we demonstrated that the treatment with
DEX plus a monoclonal antibody to the human IGF-1 receptor (αIGF-1R)
leads to the down-regulation of the gene expression of
Bcl-xL, an antiapoptotic gene, and the activation of
CPP32 during this apoptotic process. IFN-α as well as IL-6 prevented
DEX plus αIGF-1R-induced apoptosis, and this prevention was blocked
by the mitogen-activated protein kinase kinase inhibitor, PD098059, or
the phosphatidylinositol 3-kinase inhibitor, wortmannin. Therefore,
both IL-6 and IFN-α blocked DEX plus αIGF-1R-induced apoptosis
through activation of the mitogen-activated protein kinase and
phosphatidylinositol 3-kinase pathways.
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