title: Pax8 modulates the expression of Wnt4 that is necessary for the maintenance of the epithelial phenotype of thyroid cells.
abstract: BACKGROUND
  The transcription factor Pax8 is expressed during thyroid development and is involved in the morphogenesis of the thyroid gland and maintenance of the differentiated phenotype. In particular, Pax8 has been shown to regulate genes that are considered markers of thyroid differentiation. Recently, the analysis of the gene expression profile of FRTL-5 differentiated thyroid cells after the silencing of Pax8 identified Wnt4 as a novel target. Like the other members of the Wnt family, Wnt4 has been implicated in several developmental processes including regulation of cell fate and patterning during embryogenesis. To date, the only evidence on Wnt4 in thyroid concerns its down-regulation necessary for the progression of thyroid epithelial tumors.
  
  
  RESULTS
  Here we demonstrate that Pax8 is involved in the transcriptional modulation of Wnt4 gene expression directly binding to its 5'-flanking region, and that Wnt4 expression in FRTL-5 cells is TSH-dependent. Interestingly, we also show that in thyroid cells a reduced expression of Wnt4 correlates with the alteration of the epithelial phenotype and that the overexpression of Wnt4 in thyroid cancer cells is able to inhibit cellular migration.
  
  
  CONCLUSIONS
  We have identified and characterized a functional Pax8 binding site in the 5'-flanking region of the Wnt4 gene and we show that Pax8 modulates the expression of Wnt4 in thyroid cells. Taken together, our results suggest that in thyroid cells Wnt4 expression correlates with the integrity of the epithelial phenotype and is reduced when this integrity is perturbed. In the end, we would like to suggest that the overexpression of Wnt4 in thyroid cancer cells is able to revert the mesenchymal phenotype.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Filippone
authors.forename: Tina
authors.initials: T
authors.lastname: Di Palma
authors.forename: Valeria
authors.initials: V
authors.lastname: Lucci
authors.affiliation: IEOS - Institute of Experimental Endocrinology and Oncology CNR - National Research Council, via S, Pansini 5, 80131 Naples, Italy. s.zannini@ieos.cnr.it.
authors.forename: Mariastella
authors.initials: M
authors.lastname: Zannini
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D051381:Rats; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013972:Thyrotropin / Q000378:metabolism; D060528:Wnt4 Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; C499497:Pax8 protein, rat; D060528:Wnt4 Protein; C555583:Wnt4 protein, rat; D013972:Thyrotropin