title: Induction of TTF-1 or PAX-8 expression on proliferation and tumorigenicity in thyroid carcinomas.
abstract: TTF-1 and PAX-8 are responsible for thyroid organogenesis and for maintenance of differentiation in thyrocytes. Thus, we hypothesized that the induction of these two transcription factors could affect proliferation and tumorigenicity. Moreover, the ability of various pharmacological agents to modulate expression of the TTF-1 and PAX-8 and their effects on apoptosis were also analysed. For this purpose, cell lines derived from papillary (TPC-1 and BHP 10-3) and anaplastic (ARO) thyroid carcinomas were stably transfected with expression vectors containing TTF-1 or PAX-8 genes. Subsequently, the effects on expression at gene and protein levels, as well as on cell growth, cell cycle, migration and in vivo tumorigenicity were studied. Our results showed that: i) TTF-1 reciprocally induces PAX-8 expression; ii) the basal state of TTF-1 or PAX-8 influences proliferation, migration and tumorigenicity; iii) the induction of TTF-1 acts on cell proliferation more than PAX-8 and mainly affects tumorigenicity; and iv) TTF-1 was found to be more sensitive to epigenetic modulators than PAX-8. Therefore, we postulated that both TTF-1 and PAX-8 when co-expressed have anti-proliferative and anti-tumorigenic properties up to a threshold expression level and beyond that, are able to induce pro-tumorigenic effects. Hence in future, it will be quite interesting to systematically take into account the basal state of expression of TTF-1 and PAX-8. It will also be important to study the two thyroid transcription factors as part of a duo. This could open in the long-term, new therapeutic perspectives for thyroid carcinomas.
authors: Vectorology and Anticancer Therapies, UMR 8203 CNRS, Université Paris-Sud, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France.
authors: Célia
authors: C
authors: Dupain
authors: Vectorology and Anticancer Therapies, UMR 8203 CNRS, Université Paris-Sud, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France.
authors: Hafiz M
authors: HM
authors: Ali
authors: Vectorology and Anticancer Therapies, UMR 8203 CNRS, Université Paris-Sud, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France.
authors: Tarik Ait
authors: TA
authors: Mouhoub
authors: Vectorology and Anticancer Therapies, UMR 8203 CNRS, Université Paris-Sud, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France.
authors: Giorgia
authors: G
authors: Urbinati
authors: Vectorology and Anticancer Therapies, UMR 8203 CNRS, Université Paris-Sud, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France.
authors: Liliane
authors: L
authors: Massaad-Massade
mesh_terms: D000818:Animals; D017209:Apoptosis; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002291:Carcinoma, Papillary; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D000072636:PAX8 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D065646:Thyroid Carcinoma, Anaplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C000614412:NKX2-1 protein, human; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors