Induction of ETS-1 and ETS-2 transcription factors is required for thyroid cell transformation.
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.
Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli, Naples, Italy.
F
F
de Nigris
T
T
Mega
N
N
Berger
M V
MV
Barone
M
M
Santoro
G
G
Viglietto
P
P
Verde
A
A
Fusco
D017209:Apoptosis / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D016384:Consensus Sequence; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000502:physiology; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000096:biosynthesis* / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494041:ETS1 protein, human; C494069:ETS2 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA