The promoter of the human sodium/iodide-symporter gene responds to retinoic acid

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:189

Article

Schmutzler, C ; Schmitt, TL ; Glaser, F ; Loos, U ; Köhrle, J

关键词: thyroid carcinoma;    redifferentiation;    iodide transport;    radioiodide therapy;    nuclear receptor;   

DOI  :  10.1016/S0303-7207(01)00735-3

来源: Elsevier

【 摘 要 】

It was shown previously that hNIS mRNA expression is stimulated by retinoic acid (RA) in human follicular thyroid carcinoma cell lines FTC-133 and FTC-238. and patients with thyroid carcinomas lacking iodide uptake respond to RA treatment with increased radioiodide transport. Here, in transient transfection experiments using FTC-238 cells, hNIS promoter/luciferase reporter constructs showed an up to 2.5-fold increase in transcriptional activity after incubation with 1 muM RA. Stimulation by 10 nM T3 was up to 2.4-fold. Deletion or block mutation of a putative nuclear receptor recognition site. 'DR10', abolished RA and T3 responses. Four copies of the DR10 cloned 5' to the thymidine kinase promoter gave a 2.6-fold and a 1.4-fold increase in transcriptional activity after RA and T3 stimulation, respectively. In electrophoretic mobility shifts, a wildtype DR10 oligonucleotide, but not block mutants of either DR10 halfsite, interacted with nuclear receptors. Thus, RA redifferentiation of advanced thyroid carcinomas may reinduce iodide uptake by stimulating hNIS expression and thereby make tumours accessible for radioiodide therapy again. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

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