The sodium iodide symporter (NIS): Regulation and approaches to targeting for cancer therapeutics

Kogai, Takahiko; Brent, Gregory A.

doi:10.1016/j.pharmthera.2012.06.007

Cited by 151 publications

(149 citation statements)

References 196 publications

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“…Characterization of the elements that regulate TSHR (Kakinuma et al 1996) and NIS (Chiefari et al 2002) expression has stimulated/facilitated attempts to identify the roles these genes play in human thyroid cancer. Most studies have found that NIS expression in thyroid cancers is reduced or absent (except for some cases with defective membrane transport) (Kogai & Brent 2012), whereas TSHR expression in these tumors is often preserved (Brabant et al 1991, Ohta et al 1991, Lazar et al 1999, Sheils & Sweenwy 1999, Tanaka et al 2000, Durante et al 2007; Sponziello, Durante C, Russo D & Filetti S, 2013, unpublished observations). The latter property of most thyroid cancers, combined with the TSH stimulation of NIS expression and function, has been and is currently exploited for the TSH-induced radioiodine conventional treatment of differentiated thyroid malignancies (Schlumberger et al 2007, Wartofsky & Van Nostrand 2012.…”

Section: Discussionmentioning

confidence: 95%

“…Radioactive iodine is the most effective method for managing recurrent and metastatic disease in these patients, but it requires adequate tumor tissue expression of genes that play key roles in iodine metabolism, in particular those encoding the thyroid-stimulating hormone receptor (TSHR) and the sodium/iodide symporter (NIS) (Schlumberger et al 2007, Wartofsky & Van Nostrand 2012. Many studies have demonstrated losses/reductions in NIS (SLC5AS) expression and function in primary and metastatic thyroid cancer cells as a result of oncogenic activation (Trapasso et al 1999, Arturi et al 2000, Puxeddu et al 2008, Kogai & Brent 2012. Alterations involving the ras-RAF-MAPK and PI3K-AktmTOR signal transduction pathways have been shown to play major roles in these changes (Xing 2010).…”

Section: Introductionmentioning

confidence: 99%

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Different expression of TSH receptor and NIS genes in thyroid cancer: role of epigenetics

D’Agostino¹,

Sponziello²,

Puppin³

et al. 2013

Journal of Molecular Endocrinology

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The TSH receptor (TSHR) and sodium/iodide symporter (NIS) are key players in radioiodinebased treatment of differentiated thyroid cancers. While NIS (SLC5AS) expression is diminished/lost in most thyroid tumors, TSHR is usually preserved. To examine the mechanisms that regulate the expression of NIS and TSHR genes in thyroid tumor cells, we analyzed their expression after inhibition of ras-BRAF-MAPK and PI3K-Akt-mTOR pathways and the epigenetic control occurring at the gene promoter level in four human thyroid cancer cell lines. Quantitative real-time PCR was used to measure NIS and TSHR mRNA in thyroid cancer cell lines (TPC-1, BCPAP, WRO, and FTC-133). Western blotting was used to assess the levels of total and phosphorylated ERK and Akt. Chromatin immunoprecipitation was performed for investigating histone post-translational modifications of the TSHR and NIS genes. ERK and Akt inhibitors elicited different responses of the cells in terms of TSHR and NIS mRNA levels. Akt inhibition increased NIS transcript levels and reduced those of TSHR in FTC-133 cells but had no significant effects in BCPAP. ERK inhibition increased the expression of both genes in BCPAP cells but had no effects in FTC-133. Histone posttranslational modifications observed in the basal state of the four cell lines as well as in BCPAP treated with ERK inhibitor and FTC-133 treated with Akt inhibitor show cell-and gene-specific differences. In conclusion, our data indicate that in thyroid cancer cells the expression of TSHR and NIS genes is differently controlled by multiple mechanisms, including epigenetic events elicited by major signaling pathways involved in thyroid tumorigenesis.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Different expression of TSH receptor and NIS genes in thyroid cancer: role of epigenetics

D’Agostino¹,

Sponziello²,

Puppin³

et al. 2013

Journal of Molecular Endocrinology

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“…It is mentioned that NIS protein must be expressed in basolateral membranes of thyroid follicular epithelium in order to function (7,8).…”

Section: Introductionmentioning

confidence: 99%

Sodium Iodide Symporter Protein Expression and Clinicopathological Variables in Pure Testicular Seminomas

Yazgan¹,

Ener²,

Gözalan³

et al. 2017

Cyprus J Med Sci

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BACKGROUNDTestis carcinomas cause cancer-related morbidity and mortality in adults. Radioiodine I-131 (RAI) therapy may be an alternative for the treatment. The aim of this study is to investigate the presence and localization of sodium iodide symporter (NIS) expression in pure testicular seminomas, two lymph nodes with seminoma metastasis, and two embryonal carcinomas by immunohistochemically methods. MATERIAL and METHODSThe localization of NIS expression was defined as positive according to >10% membranous staining. Cytoplasmic staining was noted as present/absent. NIS expression was compared to the invasions. RESULTSThere was no rete testis invasion in 66.7% (26/37) and epididymis invasion in 84.6% (33/37) of the cases. Lymphovascular invasion was seen in 64.1% (25/37) of the cases. There was no membranous staining in pure seminomas, but it was present in two embryonal carcinomas. Cytoplasmic staining was present in 41% (16/34) of the tumors. Cytoplasmic NIS expression was present in 72.7% (p=0.135) and 75% (p=0.6) of the rete testis and epididymis invasions, respectively. There was no statistically important relationship with the cytoplasmic expression, lymphovascular invasion, and the other parameters (p>0.05). CONCLUSIONResearch of NIS expression in pure seminomas with larger series may clear the option of RAI treatment in seminomas. Also, evidence of different expression profiles in non-seminomatous testicular tumors was determined.

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“…In the present study two different types of tracers were used, 99 m Tc-pertechnetate and 99 m Tc-MIBI. As a substrate of the sodium iodide symporter [22] duction of tracer uptake in thyroid tissue volume after microwave ablation. This can be explained by the effect of microwave ablation as a thermal treatment.…”

mentioning

confidence: 99%

“…These effects are most likely to occur on molecular and not structural levels. Tracer uptake is based on molecular processes, as described by Kogai et al [22] and Arbab et al [26], and may display necrosis even before struc- tural alterations happen. Therefore, it makes even early-stage evaluation feasible.…”

mentioning

confidence: 99%

Diagnostic Accuracy of Elastography and Scintigraphic Imaging After Thermal Microwave Ablation of Thyroid Nodules

Korkusuz

Happel

Klebe

et al. 2015

Fortschr Röntgenstr

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!Purpose: The aim of this study is to evaluate structural alterations of thyroid tissue after microwave ablation using elastography and scintigraphic imaging to investigate the applicability of these diagnostic methods for follow-up. Materials and Methods: 35 patients with 39 thyroid nodules were evaluated using elastography and scintigraphic imaging before and after ultrasound-guided microwave ablation. Elastography was analyzed according to color-coded output and results were classified using a fourfold elasticity score (ES). Nodules color-coded blue were classified ES1 for high elasticity through ES2 and ES3 for lower elasticity, and nodules with very low elasticity were color-coded red and classified as ES4. 99m Tc-pertechnetate served as a tracer for scintigraphic imaging of hot and indifferent nodules and 99m Tc-MIBI for cold nodules. Results: Before microwave ablation, elastography detected a median elasticity score of ES 2 ± 0.7, and after ablation the median score was ES 3 ± 0.6. Overall, the median score increased by 1ES ± 0.6 (p < 0.01). Scintigraphic imaging detected a median reduction of tracer uptake in ablated tissue of 38.7 %± 27.5(p < 0.01). 99m Tc-pertechnetate scans showed a median decrease of tracer uptake of 26.3 %± 16.3 and 99m Tc-MIBI scans detected uptake reduction of 54.7 %± 29.2. Conclusion: Scintigraphic imaging using 99m Tcpertechnetate and 99m Tc-MIBI provides quantifiable results and is promising as a diagnostic follow-up after microwave ablation. Strain elastography detects decreasing tissue elasticity, but accuracy is limited by the necessary reduction of color-coded output to elasticity scores.

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The sodium iodide symporter (NIS): Regulation and approaches to targeting for cancer therapeutics

Cited by 151 publications

References 196 publications

Different expression of TSH receptor and NIS genes in thyroid cancer: role of epigenetics

Different expression of TSH receptor and NIS genes in thyroid cancer: role of epigenetics

Sodium Iodide Symporter Protein Expression and Clinicopathological Variables in Pure Testicular Seminomas

Diagnostic Accuracy of Elastography and Scintigraphic Imaging After Thermal Microwave Ablation of Thyroid Nodules

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