title: Functional inactivation of thyroid transcription factor-1 in PCCl3 thyroid cells.
abstract: Thyroid transcription factor-1 (TTF-1) is a key regulator of thyroid development and function. In order to identify the genes whose expression depends on TTF-1 transcriptional activity within the thyrocyte we analyzed the consequence of the functional inactivation of this factor in PCCl3 cells. The expression of a fusion protein composed of the DNA binding domain of TTF-1 and of the strong repressive domain of the engrailed protein resulted in a dramatic loss of epithelial cell morphology and in proliferation arrest. These changes were reversed when the inhibition of endogenous TTF-1 was relieved. No change was observed when a similar fusion protein containing point mutations abolishing DNA binding activity was produced in the cells. Besides the expected down-regulation of expression of the main genes linked to the differentiated thyroid function, we observed a decreased expression of the transcription factors Hhex, Pax 8 and TTF-2 and of E-cadherin. By contrast, both ThOX-1 and DUOXA-1 genes were up-regulated, as well as the ones encoding vimentin and several proteins involved in cell cycle arrest. Our data thus extend the known roles of TTF-1 in thyroid development and in the expression of differentiated function in the adult organ to the control of epithelial morphology and of cell division in mature thyrocytes.
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, IBMM, Biopark Charleroi Brussels South, B-6041 Gosselies, Belgium.
authors.forename: Christiane
authors.initials: C
authors.lastname: Christophe-Hobertus
authors.forename: Anne
authors.initials: A
authors.lastname: Lefort
authors.forename: Frederick
authors.initials: F
authors.lastname: Libert
authors.forename: Daniel
authors.initials: D
authors.lastname: Christophe
mesh_terms: D000818:Animals; D019556:COS Cells; D015820:Cadherins / Q000096:biosynthesis; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics; D000074623:Dual Oxidases; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D018816:Genes, cdc; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D019255:NADPH Oxidases / Q000096:biosynthesis; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000096:biosynthesis; D011401:Promoter Regions, Genetic; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D014746:Vimentin / Q000096:biosynthesis
chemical_list: D015820:Cadherins; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C526350:FoxE1 protein, rat; C513079:Hhex protein, rat; D018398:Homeodomain Proteins; C000614412:NKX2-1 protein, human; C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C499497:Pax8 protein, rat; D011993:Recombinant Fusion Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D014746:Vimentin; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C524752:Duox1 protein, rat