Abstract
As survival regulation is a key process in multiple myeloma biology, we have studied the Bcl-2 family proteins that can be regulated by three myeloma cell survival factors: interleukin-6 (IL-6), interferon-alpha (IFN-alpha) and insulin-like growth factor (IGF-1). Eleven myeloma cell lines, whose survival and proliferation are dependent on addition of IL-6, variably expressed 10 anti-apoptotic or pro-apoptotic proteins of the Bcl-2-family. When myeloma cells from four cell lines were IL-6 starved and activated with IL-6 or IFN-alpha, we observed that only Mcl-1 expression was up-regulated with myeloma cell survival induction. Nor was obvious regulation of these 10 pro-apoptotic or anti-apoptotic proteins found with IGF-1, another potent myeloma cell survival factor. Our results indicate that the myeloma cell survival activity of IL-6 linked to Bcl-xL regulation cannot be generalized and emphasize that Mcl-1 is the main target of IL-6 and IFN-alpha stimulation. However, other changes in the activity of the Bcl-2 protein family or other apoptosis regulators must be identified to elucidate the IGF-1 action mechanism. Cell Death and Differentiation (2000) 7, 1244 - 1252.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Survival / drug effects
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Cell Survival / physiology*
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DNA-Binding Proteins / drug effects
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / physiology
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Humans
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Insulin-Like Growth Factor I / metabolism
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Insulin-Like Growth Factor I / pharmacology*
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Interferon-alpha / metabolism
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Interferon-alpha / pharmacology*
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Interleukin-6 / metabolism
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Interleukin-6 / pharmacology*
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Multiple Myeloma / genetics
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Multiple Myeloma / metabolism*
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Multiple Myeloma / physiopathology
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Myeloid Cell Leukemia Sequence 1 Protein
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Neoplasm Proteins / drug effects
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Neoplasm Proteins / metabolism
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Plasma Cells / drug effects
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Plasma Cells / metabolism
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Plasma Cells / pathology
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Proto-Oncogene Proteins c-bcl-2 / drug effects
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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STAT3 Transcription Factor
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Trans-Activators / drug effects
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Trans-Activators / metabolism
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Tumor Cells, Cultured / cytology
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / metabolism*
Substances
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DNA-Binding Proteins
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Interferon-alpha
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Interleukin-6
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Myeloid Cell Leukemia Sequence 1 Protein
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Neoplasm Proteins
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Proto-Oncogene Proteins c-bcl-2
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STAT3 Transcription Factor
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STAT3 protein, human
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Trans-Activators
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Insulin-Like Growth Factor I