Sodium Iodide Symporter (NIS) Gene Expression in Human Placenta

Placenta ◽  
2001 ◽  
Vol 22 (2-3) ◽  
pp. 256-258 ◽  
Author(s):  
A.M Mitchell ◽  
S.W Manley ◽  
J.C Morris ◽  
K.A Powell ◽  
E.R Bergert ◽  
...  
2010 ◽  
Vol 3 (1) ◽  
pp. 3 ◽  
Author(s):  
Md. Harun-Or-Rashid ◽  
Masato Asai ◽  
Xiao-yang Sun ◽  
Yoshitaka Hayashi ◽  
Junichi Sakamoto ◽  
...  

2007 ◽  
Vol 92 (1) ◽  
pp. 70-76 ◽  
Author(s):  
Gabor Szinnai ◽  
Ludovic Lacroix ◽  
Aurore Carré ◽  
Fabien Guimiot ◽  
Monique Talbot ◽  
...  

2006 ◽  
Vol 13 (3) ◽  
pp. 797-826 ◽  
Author(s):  
T Kogai ◽  
K Taki ◽  
G A Brent

The sodium/iodide symporter (NIS) mediates iodide uptake in the thyroid gland and lactating breast. NIS mRNA and protein expression are detected in most thyroid cancer specimens, although functional iodide uptake is usually reduced resulting in the characteristic finding of a ‘cold’ or non-functioning lesion on a radioiodine image. Iodide uptake after thyroid stimulating hormone (TSH) stimulation, however, is sufficient in most differentiated thyroid cancer to utilize β-emitting radioactive iodide for the treatment of residual and metastatic disease. Elevated serum TSH, achieved by thyroid hormone withdrawal in athyreotic patients or after recombinant human thyrotropin administration, directly stimulates NIS gene expression and/or NIS trafficking to the plasma membrane, increasing radioiodide uptake. Approximately 10–20% differentiated thyroid cancers, however, do not express the NIS gene despite TSH stimulation. These tumors are generally associated with a poor prognosis. Reduced NIS gene expression in thyroid cancer is likely due in part, to impaired trans-activation at the proximal promoter and/or the upstream enhancer. Basal NIS gene expression is detected in about 80% breast cancer specimens, but the fraction with functional iodide transport is relatively low. Lactogenic hormones and various nuclear hormone receptor ligands increase iodide uptake in breast cancer cells in vitro, but TSH has no effect. A wide range of ‘differentiation’ agents have been utilized to stimulate NIS expression in thyroid and breast cancer using in vitro and in vivo models, and a few have been used in clinical studies. Retinoic acid has been used to stimulate NIS expression in both thyroid and breast cancer. There are similarities and differences in NIS gene regulation and expression in thyroid and breast cancer. The various agents used to enhance NIS expression in thyroid and breast cancer will be reviewed with a focus on the mechanism of action. Agents that promote tumor differentiation, or directly stimulate NIS gene expression, may result in iodine concentration in ‘scan-negative’ thyroid cancer and some breast cancer.


Endocrinology ◽  
2004 ◽  
Vol 145 (3) ◽  
pp. 1290-1293 ◽  
Author(s):  
Cinzia Puppin ◽  
Franco Arturi ◽  
Elisabetta Ferretti ◽  
Diego Russo ◽  
Rosario Sacco ◽  
...  

Abstract The transcriptional regulation of the human sodium/iodide symporter (NIS) gene in normal and transformed thyroid cells is a crucial issue in attempting to restore iodide uptake and use radioiodine as a therapeutic treatment of thyroid cancer. Previous investigations have shown that the multifunctional protein apurinic apyrimidinic endonuclease/redox factor 1 (APE/Ref-1) plays an important role in regulation of thyroid-specific gene transcription. In this study, we investigated the effects of APE/Ref-1 on human NIS promoter activity. Cotransfection experiments performed in nonthyroid HeLa cells demonstrated that APE/Ref-1 exerts both PAX8-dependent and PAX8-independent effects. In fact, in the absence of PAX8, overexpression of APE/Ref-1 enhanced NIS promoter activity 2-fold. When the expression plasmid of APE/Ref-1 was transfected together with an expression plasmid for PAX8, a strong cooperative effect was detected with an increase of NIS promoter activity 9-fold over control. The PAX8-independent effect of APE/Ref-1 was specific for the NIS promoter, resulting not present for the promoter of the thyroperoxidase (TPO) gene. It was, at least in part, due to the up-regulation of the transcriptional activity of the ubiquitous factor early growth response-1 (Egr-1). In the thyroid tumor cell lines TPC-1 and B-CPAP, APE/Ref-1 was not effective by itself, and it also failed to increase PAX8 stimulation on NIS promoter activity. These data demonstrate a role for APE/Ref-1 protein in the transcriptional regulation of NIS gene expression by itself and in cooperation with PAX8. However, restoring the PAX8-APE/Ref-1 expression in tumor cells may not be sufficient to obtain adequate levels of NIS gene expression.


2007 ◽  
Vol 6 (7) ◽  
pp. 1130-1135 ◽  
Author(s):  
Hyun Joo Kim ◽  
Yong Hyun Jeon ◽  
Joo Hyun Kang ◽  
Yong Jin Lee ◽  
Kwang Kim ◽  
...  

2007 ◽  
Vol 51 (5) ◽  
pp. 672-682 ◽  
Author(s):  
Denise P. Carvalho ◽  
Andrea C.F. Ferreira

The thyroid gland has the ability to uptake and concentrate iodide, which is a fundamental step in thyroid hormone biosynthesis. Radioiodine has been used as a diagnostic and therapeutic tool for several years. However, the studies related to the mechanisms of iodide transport were only possible after the cloning of the gene that encodes the sodium/iodide symporter (NIS). The studies about the regulation of NIS expression and the possibility of gene therapy with the aim of transferring NIS gene to cells that normally do not express the symporter have also become possible. In the majority of hypofunctioning thyroid nodules, both benign and malignant, NIS gene expression is maintained, but NIS protein is retained in the intracellular compartment. The expression of NIS in non-thyroid tumoral cells in vivo has been possible through the transfer of NIS gene under the control of tissue-specific promoters. Apart from its therapeutic use, NIS has also been used for the localization of metastases by scintigraphy or PET-scan with 124I. In conclusion, NIS gene cloning led to an important development in the field of thyroid pathophysiology, and has also been fundamental to extend the use of radioiodine for the management of non-thyroid tumors.


2007 ◽  
Vol 92 (10) ◽  
pp. 4046-4051 ◽  
Author(s):  
Huika Li ◽  
Kerry Richard ◽  
Brett McKinnon ◽  
Robin H. Mortimer

Abstract Context: Active placental transport of maternal iodide by the thyroidal sodium iodide symporter (NIS) provides an essential substrate for fetal thyroid hormone synthesis. NIS is expressed in trophoblast and is regulated by human choriogonadotropin (hCG). In thyroid, iodide down-regulates expression of several genes including NIS. Placentas of iodine-deficient rats demonstrate up-regulation of NIS mRNA, suggesting a role for iodide in regulating placental NIS. Objectives and Methods: The objectives were to examine effects of iodide on expression of NIS and hCG in BeWo choriocarcinoma cells. Gene expression was studied by quantitative real-time PCR. Effects on NIS protein expression were assessed by Western blotting. Functional activity of NIS was measured by 125I uptake. Expression of hCG protein was assessed by immunoassay of secreted hormone. Results: Iodide inhibited NIS mRNA and membrane protein expression as well as 125I uptake, which were paralleled by decreased βhCG mRNA expression and protein secretion. Iodide had no effects on pendrin expression. Addition of hCG increased NIS mRNA expression. This effect was partially inhibited by addition of iodide. The inhibitory effects of iodide on NIS mRNA expression were abolished by propylthiouracil and dithiothreitol. Conclusions: We conclude that expression of placental NIS is modulated by maternal iodide. This may occur through modulation of hCG effects on NIS and hCG gene expression.


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