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Reactive Oxygen Species Are Critical for the Growth and Differentiation of Medullary Thyroid Carcinoma Cells¹

The Oncology Center Research Laboratories, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231

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:Raf-1:ER. Catalase, but not Cu/Zn superoxide dismutase, completely inhibited Raf-1-induced differentiation of ß-estradiol-treated TT:Raf-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:Raf-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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