Abstract
A new human myeloma cell line, OPM-6, was established from the peripheral blood of a patient with advanced IgG-kappa 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 (alphaIGF-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-alpha as well as IL-6 prevented DEX plus alphaIGF-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-alpha blocked DEX plus alphaIGF-1R-induced apoptosis through activation of the mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Apoptosis / drug effects*
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Apoptosis / genetics
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Caspase 3
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Caspases / metabolism
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Dexamethasone / antagonists & inhibitors*
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Dexamethasone / toxicity
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Insulin-Like Growth Factor I / antagonists & inhibitors
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Insulin-Like Growth Factor I / biosynthesis
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Insulin-Like Growth Factor I / physiology
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Interferon Type I / pharmacology*
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Interleukin-6 / pharmacology*
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MAP Kinase Signaling System / drug effects*
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MAP Kinase Signaling System / physiology
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 1 / physiology
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Multiple Myeloma / enzymology
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Multiple Myeloma / pathology*
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphatidylinositol 3-Kinases / physiology*
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Receptor, IGF Type 1 / antagonists & inhibitors
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Receptor, IGF Type 1 / physiology
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Receptor, Interferon alpha-beta
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Receptors, Interferon / physiology
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Receptors, Interleukin-6 / physiology
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Recombinant Proteins / pharmacology
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / pathology*
Substances
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Interferon Type I
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Interleukin-6
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Receptors, Interferon
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Receptors, Interleukin-6
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Recombinant Proteins
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Receptor, Interferon alpha-beta
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Insulin-Like Growth Factor I
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Dexamethasone
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Phosphatidylinositol 3-Kinases
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Receptor, IGF Type 1
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Mitogen-Activated Protein Kinase 1
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CASP3 protein, human
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Caspase 3
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Caspases