Functional inactivation of thyroid transcription factor-1 in PCCl3 thyroid cells

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• 作者：Christiane Christophe-Hobertus^a ; Anne Lefort^b ; Frederick Libert^b ; Daniel Christophe^a ; ^{dchristo@ulb.ac.be}
• 关键词：Thyroid ; Transcription ; TTF-1 ; Nkx-2.1 ; T/ebp ; Titf1
• 刊名：Molecular and Cellular Endocrinology
• 出版年：2012
• 期刊代码：109_03037207
• 类别：bio
• 出版时间：6 July, 2012
• 卷：358
• 期：1
• 页码：36-45
• 文件大小：1135 K

摘要

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.