Transcriptional activity of the 5'-flanking region of the thyroid transcription factor-1 gene in human thyroid cell lines

Abstract

Thyroid transcription factor-1 (TTF-1, NKX2-1) is a homeodomain-containing transcriptional factor that binds to and activates the promoters of thyroid and lung-specific genes, such as thyroglobulin, thyroid peroxidase, and thyroid stimulating hormone receptor. TTF-1 is known to play a key role in the development of the thyroid. However, the precise mechanism of TTF-1 gene transcription in human thyroid cells has not been studied. The expression of transcriptional activity in various lengths of the 5′-flanking region of the human TTF -1 gene was studied in TTF-1 positive and negative human thyroid cell lines. Increased transcriptional activity was observed in thyroid cell lines containing plasmids that coded for a sequence proximal to the transcription start site of exon 1 of the TTF-1 gene. However, we did not observe any difference in promoter activity in the region up to −2.6 kb from the proximal transcription start site of the TTF-1 gene between TTF-1 positive and negative cells. These results suggest that the proximal 5′-flanking region of the human TTF -1 gene does not contain sufficient cis-active regulatory information to direct gene expression in thyroid cells, and that other cis- or trans-acting factors participate in the thyroid specific gene expression of TTF-1.

Impact of Quercus infectoria Galls Extract on Thyroid Gland and Testicular Functions in Diabetic Rats

“…A possible mechanism for this might be that QIg extract markedly reduced blood glucose level, which abolishes the inhibitory effects of hyperglycemia on tight junction proteins (45) of bloodtestis barrier (BTB) (29), and thereby BTB support Sertoli cells to regulate luminal environment of a seminiferous tubule by inhibiting the permeability of cytotoxic agents (46). Furthermore, it has been shown that TTF-1 is limited to the thyroid follicular epithelial cells and play a critical role in thyroid gland epithelial cells differentiation (48), and development of thyroid glands (48), thus controlling the mechanism of cellular differentiation in thyroid gland (49). Immunochemistry results of this study revealed overexpression of TTF-1 (sum score 12) in thyroid gland of diabetic group, compared to minimal expression in normal group, which potentially influences the rate of cellular proliferation and tumorigenic potential of thyrocytes (49).…”

Radiation-Associated Small Cell Neuroendocrine Carcinoma of the Thyroid: A Case Report with Molecular Analyses

“…Among thyroid NETs, MTCs seem to consistently express TTF-1 (7,10), which is plausible because this protein is expressed in C-cells (11,12). TTF-1 is a homeodomaincontaining transcriptional factor that binds to and activates the promoters of thyroid-specific genes including TSHR, Tg, and thyroid peroxidase genes in follicular cells (13). Therefore, during carcinogenesis of SCNEC of the thyroid, the TTF-1 gene may be truncated, and the expression of some thyroidspecific genes, such as TSHR and Tg, may be regulated in a TTF-1 independent manner.…”