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Induction of ETS-1 and ETS-2 Transcription Factors Is Required for Thyroid Cell Transformation¹

Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltèa di Medicina e Chirurgia, Universitèa degli Studi di Napoli, 80131 Naples, Italy [F. d. N., M. V. B., M. S.]; Istituto Internazionale di Genetica e Biofisica, Consiglio Nazionale delle Ricerche, 80125 Naples, Italy [T. M., P. V.]; Laboratoire d’Anatomie Pathologique, Hopital de L’Antiquaille, Lyon, France [N. B.]; Istituto dei Tumori di Napoli, Fondazione Senatore Pascale, 80131 Naples, Italy [G. V.]; and Dipartimento di Medicina Sperimentale e Clinica, Facoltèa di Medicina e Chirurgia di Catanzaro, Universitèa degli Studi di Catanzaro, 88100 Catanzaro, Italy [A. F.]

The proteins of the Ets family are transcription factors involved in signal transduction, cell cycle progression, and differentiation. In this study, we report that thyroid cell neoplastic transformation is associated with a dramatic increase in ETS transcriptional activity, which is dependent on the accumulation of Ets-1, Ets-2, and other Ets-related proteins. Inhibition of ETS transactivation activity by the Ets-dominant negative construct (Ets-Z) induced programmed cell death in human thyroid carcinoma cell lines but not in normal thyroid cells. Apoptotic cell death induced by Ets-Z was dependent on the reduction of c-MYC protein levels, because it was prevented by overexpression of c-myc. Taken together, these data indicate that the induction of Ets-1 and Ets-2 transcription factors plays a pivotal role in thyroid cell neoplastic transformation.

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