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PMID: 22135066 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

An essential role for Pax8 in the transcriptional regulation of cadherin-16 in thyroid cells.

Molecular endocrinology (Baltimore, Md.) ·Vol. 26 ·No. 1 ·2012-01-00 ·Pages 67-78

de Cristofaro T, Di Palma T, Fichera I, Lucci V, Parrillo L, De Felice M, Zannini M

Abstract

Cadherin-16 was originally identified as a tissue-specific cadherin present exclusively in kidney. Only recently, Cadherin-16 has been detected also on the plasma membrane of mouse thyrocytes. This last finding prompted us to note that the expression profile of Cadherin-16 resembles that of the transcription factor Pax8, a member of the Pax (paired-box) gene family, predominantly expressed in the developing and adult kidney and thyroid. Pax8 has been extensively characterized in the thyroid and shown to be a master gene for thyroid development and differentiation. In this study, we determined the role of the transcription factor Pax8 in the regulation of Cadherin-16 expression. We demonstrate that the Cadherin-16 minimal promoter is transcriptionally active in thyroid cells as well as in kidney cells, that Pax8 is able to activate transcription from a Cadherin-16 promoter reporter construct, and more importantly, that indeed Pax8 is able to bind in vivo the Cadherin-16 promoter region. In addition, by means of Pax8 RNA interference in thyroid cells and by analyzing Pax8 null mice, we demonstrate that Pax8 regulates also in vivo the expression of Cadherin-16. Finally, we reveal that the expression of Cadherin-16 is TSH dependent in FRTL-5 thyroid cells and significantly reduced in mouse thyroid carcinomas. Therefore, we conclude that Cadherin-16 is a novel downstream target of the transcription factor Pax8, likely since the early steps of thyroid development, and that its expression is associated with the fully differentiated state of the thyroid cell.

MeSH Terms
Animals Binding Sites Cadherins/genetics,metabolism Cells, Cultured Female HeLa Cells Humans Male Mice Mice, Inbred C57BL Mice, Knockout PAX8 Transcription Factor Paired Box Transcription Factors/metabolism Promoter Regions, Genetic Protein Binding RNA Interference RNA, Small Interfering Rats Thyroid Gland/metabolism Thyroid Neoplasms/genetics,metabolism Thyrotropin/metabolism Transcription, Genetic Transcriptional Activation
Chemicals
Cadherins Cdh16 protein, mouse PAX8 Transcription Factor Paired Box Transcription Factors Pax8 protein, mouse RNA, Small Interfering Thyrotropin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
de Cristofaro Tiziana
Institute of Experimental Endocrinology and Oncology G. Salvatore, National Research Council, 80131 Napoli, Italy.
Di Palma Tina
Fichera Imma
Lucci Valeria
Parrillo Luca
De Felice Mario
Zannini Mariastella
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Article Info
Journal
Molecular endocrinology (Baltimore, Md.)
Abbr.
Mol Endocrinol
ISSN
1944-9917
DOI
10.1210/me.2011-1090
Published
2012-01-00
Epub
2011-00-01
Pages
67-78
Language
English
Region
United States
NLM ID
8801431
PMCID
PMC5417163
Subset
IM
External Links
PubMed source DOI: 10.1210/me.2011-1090 PMC Full Text
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