Characterization of a thyroid hormone-mediated short-loop feedback control of TSH receptor gene in an anaplastic human thyroid cancer cell line

in Journal of Endocrinology
Authors:
ST Chen
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JD Lin
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KH Lin
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DOI:
https://doi.org/10.1677/joe.0.1750459
Volume/Issue:
Volume 175: Issue 2
Article Type:
Other
Page Range:
459–465
Online Publication Date:
01 Nov 2002
Free access

The expression of TSH receptor (TSHR) gene is frequently lost in thyroid cancers during the process of dedifferentiation that involves perturbation of several nuclear transcription factors. We have established that thyroid hormone receptor beta1 (TRbeta1) is associated with the loss of TSHR gene expression in an anaplastic human thyroid cancer cell line, ARO. To demonstrate that TRbeta1 regulates TSHR gene expression, we performed electrophoresis mobility shift and 3,5,3'-triiodothyronine (T3) transactivation assays. As expected, TRbeta1 bound the synthesized oligomer containing TSHR promoter sequence by heterodimerizing with retinoid X receptor. When a chimeric reporter pTRCAT5'-146 enclosing the minimal TSHR promoter was applied for T3 transactivation assay, two TRbeta1-overexpressing transfectants of ARO cells (ARO1 and ARO2) demonstrated higher basal activity than their parental cells. Consequentially, T3 suppressed the reporter gene activity only in ARO1 and ARO2, but not in ARO cells. A point mutation creating a cAMP response element (CRE) in the reporter pTRCAT5'-146 CRE led to T3-induced suppression of the reporter gene in ARO cells without changing the basal or T3-induced activities in ARO1 and ARO2 cells. We conclude that the regulatory effect of T3 on TSHR gene expression is TR- and promoter DNA sequence-determined.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Page(s):
7
Article Type:
Other
Print Publication Date:
01 Nov 2002
Online Publication Date:
01 Nov 2002