Regulation of the sodium/iodide symporter by retinoids - a review

Schmutzler, Cornelia

doi:10.1055/s-2001-11017

Cited by 40 publications

(15 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is well documented that RA stimulates thyroid iodide uptake in human thyroid follicular carcinoma cells (Schmutzler 2001), thyroid cancer (Coelho et al 2004), and thyroid gland of female rats (Silva et al 2009). We now demonstrate that although 28 days of treatment with 13-cis-RA stimulates radioiodide uptake, in fact, 14 days Table 1 Effect of all-trans-retinoic acid (RA) and 13-cis-RA for 14 days in the dose of 100 mg/kg body weight (b.w.)…”

Section: Discussionmentioning

confidence: 99%

Retinoic acid modulation of thyroid dual oxidase activity in rats and its impact on thyroid iodine organification

Mühlbauer¹,

Silva²,

Marassi³

et al. 2010

Journal of Endocrinology

View full text Add to dashboard Cite

The sodium-iodide symporter (NIS) mediates iodide uptake into the thyrocytes, which is important for the diagnosis and therapy of thyroid disorders. Decreased ability to uptake iodide in thyroid carcinomas reduces the efficacy of radioiodine therapy, and retinoic acid (RA) treatment reinduces iodide uptake. The effectiveness of treatment depends not only on iodide uptake but also on the ability of thyrocytes to organify iodine, which is catalyzed by thyroperoxidase (TPO) in the presence of H 2 O 2 . Our goal was to determine the influence of RA on thyroid iodide uptake, iodine organification, and TPO and dual oxidase (DuOx) activities. Normal rats were treated with all-trans-RA or 13-cis-RA (100 or 1500 mg/100 g body weight (b.w.), s.c.) for 14 and 28 days. The 2 h thyroid radioiodine content significantly decreased in rats treated with all-trans-RA (100 mg/100 g b.w.) for 14 days. In this group, NIS function and TPO activity were unchanged, whereas DuOx activity was significantly decreased, which might have contributed to the decrease in iodine organification. Both doses of 13-cis-RA for 28 days increased the 15 min thyroid radioiodine uptake, while the 2 h radioiodide uptake increased only in rats treated with the highest dose of 13-cis-RA. While TPO activity did not change, H 2 O 2 generation was increased in this group, and serum thyroxine levels were normal. Since radioiodine half-life in the thyroid gland is important for treatment efficacy, our results highlight the importance of correctly choosing the RA isomer, the time and the dose of treatment, in order to improve the efficacy of radioiodine therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Retinoic acid modulation of thyroid dual oxidase activity in rats and its impact on thyroid iodine organification

Mühlbauer¹,

Silva²,

Marassi³

et al. 2010

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Other studies report an almost total efflux of iodine from the cells, occurring less than 1 hour after the NIS-related uptake (13)(14)(15)(16). Efflux was not significantly reduced by enzymatic or pharmacological means (14,(17)(18)(19)(20)(21)(22). Interestingly, two studies have demonstrated a long retention time for 123 I and significant tumor reduction after the application of a high dose of 131 I in NIS-transduced mice (23,24).…”

Section: Radioiodine (mentioning

confidence: 99%

Long-Term Radioiodine Retention and Regression of Liver Cancer after Sodium Iodide Symporter Gene Transfer in Wistar Rats

et al. 2004

View full text Add to dashboard Cite

Radioiodine therapy of nonthyroid cancers after sodium iodide symporter (NIS) gene delivery has been proposed as a potential application of gene therapy. However, it seems to be precluded by the rapid efflux of taken up iodine from most transduced xenografted tumors. We present an in vivo kinetic study of NIS-related hepatic iodine uptake in an aggressive model of hepatocarcinoma induced by diethylnitrosamine in immunocompetent Wistar rats. We followed the whole-body iodine distribution by repeated imaging of live animals. We constructed a rat NIS (rNIS) adenoviral vector, Ad-CMV-rNIS, using the cytomegalovirus (CMV) as a promoter. Injected in the portal vein in 5 healthy and 25 hepatocarcinoma-bearing rats and liver tumors in 9 hepatocarcinoma-bearing rats, Ad-CMV-rNIS drove expression of a functional NIS protein by hepatocytes and allowed marked (from 20 to 30% of the injected dose) and sustained (>11 days) iodine uptake. This contrasts with the massive iodine efflux found in vitro in human hepatic tumor cell lines. In vivo specific inhibition of NIS by sodium perchlorate led to a rapid iodine efflux from the liver, indicating that the sustained uptake was not attributable to an active retention mechanism but to permanent recycling of the effluent radioiodine via the high hepatic blood flow. Radioiodine therapy after Ad-CMV-rNIS administration achieved a strong inhibition of tumor growth, the complete regression of small nodules, and prolonged survival of hepatocarcinoma-bearing rats. This demonstrates for the first time the efficacy of NIS-based radiotherapy in a relevant preclinical model of nonthyroid human carcinogenesis.

show abstract

“…Retinoic acid (RA) increases iodide uptake in some differentiated thyroid cancers (33,34). Moreover, in MCF-7 breast cancer cells, all-trans RA (tRA) stimulates iodide uptake after RA receptor (RAR)-induced up-regulation of the NIS gene (17).…”

mentioning

confidence: 99%

Transcription Factor Nkx-2.5 Induces Sodium/Iodide Symporter Gene Expression and Participates in Retinoic Acid- and Lactation-Induced Transcription in Mammary Cells

Dentice

Luongo

Elefante

et al. 2004

Molecular and Cellular Biology

View full text Add to dashboard Cite

The sodium/iodide symporter (NIS) is a plasma membrane protein that mediates active iodide transport in thyroid and mammary cells. It is a prerequisite for radioiodide treatment of thyroid cancer and a promising diagnostic and therapeutic tool for breast cancer. We investigated the molecular mechanisms governing NIS expression in mammary cells. Here we report that Nkx-2.5, a cardiac homeobox transcription factor that is also expressed in the thyroid primordium, is a potent inducer of the NIS promoter. By binding to two specific promoter sites (N2 and W), Nkx-2.5 induced the rNIS promoter (about 50-fold over the basal level). Interestingly, coincident with NIS expression, Nkx-2.5 mRNA and protein were present in lactating, but not virgin, mammary glands in two human breast cancer samples and in all-trans retinoic acid (tRA)-stimulated MCF-7 breast cancer cells. A cotransfected dominant-negative Nkx-2.5 mutant abolished tRA-induced endogenous NIS induction, which shows that Nkx-2.5 activity is critical for this process. Remarkably, in MCF-7 cells, Nkx-2.5 overexpression alone was sufficient to induce NIS and iodide uptake. In conclusion, Nkx-2.5 is a novel relevant transcriptional regulator of mammary NIS and could thus be exploited to manipulate NIS expression in breast cancer treatment strategies.

show abstract

Regulation of the sodium/iodide symporter by retinoids - a review

Cited by 40 publications

References 15 publications

Retinoic acid modulation of thyroid dual oxidase activity in rats and its impact on thyroid iodine organification

Retinoic acid modulation of thyroid dual oxidase activity in rats and its impact on thyroid iodine organification

Long-Term Radioiodine Retention and Regression of Liver Cancer after Sodium Iodide Symporter Gene Transfer in Wistar Rats

Transcription Factor Nkx-2.5 Induces Sodium/Iodide Symporter Gene Expression and Participates in Retinoic Acid- and Lactation-Induced Transcription in Mammary Cells

Contact Info

Product

Resources

About