Abstract
Reactive oxygen species have recently been demonstrated to play a role in numerous cellular signal transduction pathways. Here we investigate the involvement of H2O2 in Raf-1-mediated differentiation in the human medullary thyroid carcinoma (MTC) cell line TT:deltaRaf-1:ER. Catalase, but not Cu/Zn superoxide dismutase, completely inhibited Raf-1-induced differentiation of beta-estradiol-treated TT: deltaRaf-1:ER. In addition, catalase treatment down-regulated RET expression at both the mRNA and protein levels and induced apoptosis in the parental TT cell line and uninduced TT:deltaRaf-1:ER human MTC cells. These results implicate H2O2 as a downstream mediator of c-Raf-1-induced differentiation and as a survival factor in MTC cells.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Carcinoma, Medullary / metabolism
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Carcinoma, Medullary / pathology*
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Catalase / pharmacology
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Cell Differentiation / drug effects
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Cell Differentiation / physiology
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Cell Division / physiology
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Down-Regulation
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Drosophila Proteins*
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Enzyme Activation
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Enzyme Induction
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Estradiol / pharmacology
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Hydrogen Peroxide / metabolism
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MAP Kinase Signaling System / physiology
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Mitogen-Activated Protein Kinases / metabolism
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-raf / antagonists & inhibitors
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Proto-Oncogene Proteins c-raf / biosynthesis
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Proto-Oncogene Proteins c-raf / physiology
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Proto-Oncogene Proteins c-ret
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Reactive Oxygen Species / chemistry*
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Receptor Protein-Tyrosine Kinases
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Superoxide Dismutase / pharmacology
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Thyroid Neoplasms / metabolism
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Thyroid Neoplasms / pathology*
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Tumor Cells, Cultured
Substances
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Drosophila Proteins
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Proto-Oncogene Proteins
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Reactive Oxygen Species
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Estradiol
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Hydrogen Peroxide
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Catalase
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Superoxide Dismutase
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Proto-Oncogene Proteins c-ret
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Receptor Protein-Tyrosine Kinases
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Ret protein, Drosophila
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Proto-Oncogene Proteins c-raf
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Mitogen-Activated Protein Kinases