Study of TTF-1 gene expression in dog thyrocytes in primary culture

Renterghem, Pierre Van; Dremier, Sarah; Vassart, Gilbert; Christophe, Daniel

doi:10.1016/0303-7207(95)03589-y

Cited by 35 publications

(19 citation statements)

References 25 publications

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“…Both in rat (as we have demonstrated in this study) and in dog (Van Renterghem et al 1995), TSH up-regulates Pax-8 expression. Therefore, Pax-8 protein levels could represent an important determinant by which TSH regulates thyroid cells.…”

Section: Discussionsupporting

confidence: 76%

Pax-8 protein levels regulate thyroglobulin gene expression

Fabbro

Pellizzari²,

Mercuri³

et al. 1998

Journal of Molecular Endocrinology

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Pax proteins are transcription factors that control differentiation of several cell types. In adult organisms Pax-8 is expressed in the follicular thyroid cell where it interacts with sequences of thyroglobulin and thyroperoxidase promoters. In this study, we provide evidence indicating that Pax-8 protein levels regulate thyroglobulin gene transcription. The most critical approach consisted in increasing Pax-8 protein levels by transfecting thyroid cells with a Pax-8 expression vector. In this situation the thyroglobulin promoter transcriptional activity was significantly increased with respect to untransfected cells. In contrast, the transfection of thyroid transcription factor-1 (TTF-1) expression vector causes a modest decrease of thyroglobulin promoter activity, rather than an increase. Northern blots of human papillary cancers reveal a significant correlation between Pax-8 and thyroglobulin mRNAs. Gel-retardation assays suggest that the mechanism by which the Pax-8 protein levels modulate thyroglobulin promoter activity may occur through competition with TTF-1 for a common binding site. Since we also demonstrate that Pax-8 expression is subjected to TSH control, our data strongly suggest that Pax-8 protein levels could represent an important determinant for the regulation of thyroid cells.

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Section: Discussionsupporting

confidence: 76%

Pax-8 protein levels regulate thyroglobulin gene expression

Fabbro

Pellizzari²,

Mercuri³

et al. 1998

Journal of Molecular Endocrinology

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“…In the same studies (124,134), both TTF-1 and Pax-8 were shown to be phosphorylated nuclear proteins in control cells. No dramatic change in their phosphorylation could be detected following cAMP stimulation, which at first argues against the possibility that cAMP-dependent Tg gene transcription relies essentially on PKA-mediated phosphorylation of one, or both, of these factors.…”

Section: Expression Of Thyroid-specific Transcription Factorsmentioning

confidence: 77%

“…Mutagenesis experiments revealed that thyroid transcription factor-1 (TTF-1) (121) plays a major role in the transcriptional activity of the Tg promoter (122). However, whether TTF-1 is only required for basal promoter activity or whether it mediates the effect of cAMP remained an open question (123,124), as the very low level of transcriptional activity of the promoters when transfected in unstimulated cells precluded a clear demonstration of the role of TTF-1 in this basal activity. The DNA sequences corresponding to the upstream hypersensitive site in bovine Tg gene chromatin (see earlier section on chromatin structure of the Tg gene) were shown to exhibit enhancer activity when assayed in transfected dog thyrocytes (125).…”

Section: Promoter Regions Of Tg and Tpo Genesmentioning

confidence: 99%

“…Their expression was studied at RNA and protein levels in the primary cultured dog thyrocytes maintained in dedifferentiating (EGF+serum), control and cAMP-stimulated (forskolin) conditions (124,134). Both factors are less abundant in dedifferentiated cells (EGF+serum conditions) than in the control cells.…”

Section: Expression Of Thyroid-specific Transcription Factorsmentioning

confidence: 99%

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The dog thyroid primary culture system: a model of the regulation of function, growth and differentiation expression by cAMP and other well-defined signaling cascades

Roger¹,

Christophe²,

Dumont³

et al. 1997

European Journal of Endocrinology

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“…In the dog, particularly, there are large numbers of C cells, and these cells express much higher levels of TTF-1 RNA in vivo than thyroid follicular epithelia (61). This fact may explain why TSH-cAMP does not appear to suppress TSHR gene expression in primary cultures of dog thyrocytes and may contribute to apparent species specificity (38,64). The functional role of TTF-1 is, therefore, best studied in cell lines FRTL-5 or rMTC, where no ambiguity exists as to cell type.…”

Section: Discussionmentioning

confidence: 99%

Thyroid Transcription Factor 1 Is Calcium Modulated and Coordinately Regulates Genes Involved in Calcium Homeostasis in C Cells

Suzuki

Lavaroni

Mori

et al. 1998

Molecular and Cellular Biology

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Thyroid transcription factor 1 (TTF-1) was identified for its critical role in thyroid-specific gene expression; its level in the thyroid is regulated by thyrotropin-increased cyclic AMP levels. TTF-1 was subsequently found in lung tissue, where it regulates surfactant expression, and in certain neural tissues, where its function is unknown. Ligands or signals regulating TTF-1 levels in lung or neural tissue are unknown. We recently identified TTF-1 in rat parafollicular C cells and parathyroid cells. In this report, we show that TTF-1 is present in the parafollicular C cells of multiple species and that it interacts with specific elements on the 5-flanking regions of the extracellular Ca 2؉ -sensing receptor (CaSR), calmodulin, and calcitonin genes in C cells. When intracellular Ca 2؉ levels are increased or decreased in C cells, by the calcium ionophore A23187, by physiologic concentrations of the P 2 purinergic receptor ligand ATP, or by changes in extracellular Ca 2؉ levels, the promoter activity, RNA levels, and binding of TTF-1 to these genes are, respectively, decreased or increased. The changes in TTF-1 inversely alter CaSR gene and calcitonin gene expression. We show, therefore, that TTF-1 is a Ca 2؉ -modulated transcription factor that coordinately regulates the activity of genes critical for Ca 2؉ homeostasis by parafollicular C cells. We hypothesize that TTF-1 similarly coordinates Ca 2؉ -dependent gene expression in all cells in which TTF-1 and the CaSR are expressed, i.e., parathyroid cells, neural cells in the anterior pituitary or hippocampus, and keratinocytes.

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Study of TTF-1 gene expression in dog thyrocytes in primary culture

Cited by 35 publications

References 25 publications

Pax-8 protein levels regulate thyroglobulin gene expression

Pax-8 protein levels regulate thyroglobulin gene expression

The dog thyroid primary culture system: a model of the regulation of function, growth and differentiation expression by cAMP and other well-defined signaling cascades

Thyroid Transcription Factor 1 Is Calcium Modulated and Coordinately Regulates Genes Involved in Calcium Homeostasis in C Cells

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