Reactive oxygen species are critical for the growth and differentiation of medullary thyroid carcinoma cells.
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.
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The Oncology Center Research Laboratories, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Thiagalingam
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Nelkin
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Casero
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D018276:Carcinoma, Medullary / Q000378:metabolism / Q000473:pathology*; D002374:Catalase / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D015536:Down-Regulation; D029721:Drosophila Proteins; D004789:Enzyme Activation; D004790:Enzyme Induction; D004958:Estradiol / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D051096:Proto-Oncogene Proteins c-ret; D017382:Reactive Oxygen Species / Q000737:chemistry*; D020794:Receptor Protein-Tyrosine Kinases; D013482:Superoxide Dismutase / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; D004958:Estradiol; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; D019908:Proto-Oncogene Proteins c-raf; D020928:Mitogen-Activated Protein Kinases