Characterization of Gastric Na+/I−Symporter of the Rat

Kotani, Takuya; Ogata, Yoshikazu; Yamamoto, Ikuo; Aratake, Yatsuki; Kawano, Junichi; Suganuma, Tatsuo; Ohtaki, Sachiya

doi:10.1006/clin.1998.4595

Cited by 43 publications

(38 citation statements)

References 22 publications

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“…In the human stomach, expression of NIS was restricted to parietal cells. Recently, characterization of rat gastric NIS by Western blot analysis showed the presence of a small amount of immature gastric NIS, with different molecular weights compared with the thyroid protein (27). This suggests the existence of tissue-specific post-translational mechanisms in the functional regulation of NIS expression.…”

Section: Nis Expression In Extrathyroidal Tissuesmentioning

confidence: 99%

“…Functional expression of the NIS gene in several extrathyroidal tissues appears to be different from that in thyroid tissue. Indeed, characterization of gastric NIS in rat shows that, whereas large amounts of NIS transcripts are expressed, little protein is detected, indicating a rapid degradation of the immature gastric NIS protein (27). In salivary glands, NIS protein is diffusely expressed within cells, suggesting a loss of the polarisation of the symporter.…”

Section: Gene Therapymentioning

confidence: 99%

See 1 more Smart Citation

Sodium/iodide symporter: a key transport system in thyroid cancer cell metabolism

Filetti¹,

Bidart

Arturi³

et al. 1999

European Journal of Endocrinology

251

144

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The recent cloning of the gene encoding the sodium/iodide symporter (NIS) has enabled better characterization of the molecular mechanisms underlying iodide transport, thus opening the way to clarifying its role in thyroid diseases. Several studies, at both the mRNA and the protein expression levels, have demonstrated that TSH, the primary regulator of iodide uptake, upregulates NIS gene expression and NIS protein abundance, both in vitro and in vivo. However, other factors, including iodide, retinoic acid, transforming growth factor-b, interleukin-1a and tumour necrosis factor a, may participate in the regulation of NIS expression. Investigation of NIS mRNA expression in different thyroid tissues has revealed increased levels of expression in Graves' disease and toxic adenomas, whereas a reduction or loss of NIS transcript was detected in differentiated thyroid carcinomas, despite the expression of other specific thyroid markers. NIS mRNA was also detected in non-thyroid tissues able to concentrate radioiodine, including salivary glands, stomach, thymus and breast.The production of specific antibodies against the NIS has facilitated study of the expression of the symporter protein. Despite of the presence of high levels of human (h)NIS mRNA, normal thyroid glands exhibit a heterogeneous expression of NIS protein, limited to the basolateral membrane of the thyrocytes. By immunohistochemistry, staining of hNIS protein was stronger in Graves' and toxic adenomas and reduced in thyroid carcinomas.Measurement of iodide uptake by thyroid cancer cells is the cornerstone of the follow-up and treatment of patients with thyroid cancer. However, radioiodide uptake is found only in about 67% of patients with persistent or recurrent disease. Several studies have demonstrated a decrease in or a loss of NIS expression in primary human thyroid carcinomas, and immunohistochemical studies have confirmed this considerably decreased expression of the NIS protein in thyroid cancer tissues, suggesting that the low expression of NIS may represent an early abnormality in the pathway of thyroid cell transformation, rather than being a consequence of cancer progression.The relationship between radioiodine uptake and NIS expression by thyroid cancer cells require further study. New strategies, based on manipulation of NIS expression, to obtain NIS gene reactivation or for use as NIS gene therapy in the treatment of radiosensitive cancer, are also being investigated. European Journal of Endocrinology 141 443-457 Role of iodine in thyroid physiology and pathophysiology Iodine in thyroid physiologyIodine represents an essential element in thyroid physiology, being a critical component of thyroxine and tri-iodothyronine molecules, and a key regulator of thyroid gland function. Thus dietary iodide supply influences the functional activity of the thyroid gland, iodine deficiency being the main cause of endemic goiter. Furthermore, iodine directly modulates thyroid sensitivity to thyroid-stimulating hormone (TSH), and intrathyroidal iodin...

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Section: Nis Expression In Extrathyroidal Tissuesmentioning

confidence: 99%

Section: Gene Therapymentioning

confidence: 99%

Sodium/iodide symporter: a key transport system in thyroid cancer cell metabolism

Filetti¹,

Bidart

Arturi³

et al. 1999

European Journal of Endocrinology

251

144

View full text Add to dashboard Cite

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“…For comparison, the stomach and lactating mammary gland were used as positive and the liver as negative controls (see Fig. 5 and other previous experiments carried out on rat (Ajjan et al 1998b, Kotani et al 1998). cDNA amplification was monitored by incorporating radioactively labelled nucleotides during the reaction.…”

Section: Tissue Expression Of Mnis Mrna In Micementioning

confidence: 99%

Cloning of the mouse sodium iodide symporter and its expression in the mammary gland and other tissues

Perron

Rodriguez²,

Leblanc³

et al. 2001

Journal of Endocrinology

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Iodide concentration in milk by mammals is a necessary step for thyroid hormone synthesis by the newborn. With the purpose of using the mouse as an animal model to analyse the role of the sodium iodide symporter (NIS) in iodide transport and its regulation in the mammary gland, mouse NIS (mNIS) cDNA was isolated from lactating mice. The cloned sequence shows an open reading frame of 1854 nucleotides encoding a protein of 618 amino acids highly homologous to the rat and human NIS (95% and 81% identity respectively). Expression of mNIS in cultured mammalian cells induced cellular iodide accumulation. This iodide uptake process is sodium dependent and inhibited by thiocyanate and perchlorate. Tissue distribution analysis revealed that mNIS mRNAs are predominantly expressed in thyroid, stomach and in the lactating mammary gland and are present to a lower extent in several other tissues. Our data show for the first time that the level of mNIS mRNA is upregulated in the mammary gland during lactation.

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“…Consequently, NIS-expressing cells will uptake radionuclides such as 131 Re, resulting in their intracellular accumulation. In tissues where NIS protein is endogenously expressed, including the thyroid, [2][3][4] stomach, 5,6 salivary gland, [7][8][9] and lactating breast, 10,11 the accumulation of these radionuclides can be detected in vivo by nuclear imaging. Use of these radioisotopes has long been essential to the diagnosis and treatment of thyroid diseases, 12 and numerous studies have been conducted to investigate the use of NISmediated radionuclide accumulation in the diagnosis and treatment of nonthyroid malignancies.…”

mentioning

confidence: 99%

Imaging of metastatic pulmonary tumors following NIS gene transfer using single photon emission computed tomography

et al. 2004

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The Na þ /I À symporter (NIS) is a membrane glycoprotein that facilitates the uptake of iodine into thyroid follicular cells. Recently, we and others have demonstrated the feasibility of imaging subcutaneous xenografts expressing exogenous NIS, suggesting that NIS may serve as an imaging reporter gene to monitor vector delivery and therapeutic gene expression. In this study, we established NIS-expressing pulmonary tumors in nude mice to investigate the minimal tumor size required for in vivo detection of pulmonary tumors by single photon emission computed tomography (SPECT) with pinhole collimation. In order to define the anatomic location of NIS-expressing tumor nodules detectable by SPECT, we performed simultaneous, dual-isotope imaging. We injected 1 mCi 99m Tc-MAA via tail vein to image pulmonary perfusion and injected 1 mCi Na 125 I intraperitoneally to image NIS-expressing tumors. Fused images showed that 99m Tc-MAA perfusion defects correlated with NIS-mediated 125 I uptake. Post-mortem analysis revealed that tumors 3 mm in diameter could be detected by SPECT with pinhole collimation. These studies demonstrate the feasibility of SPECT to detect pulmonary tumors expressing exogenous NIS in mice.

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Characterization of Gastric Na+/I−Symporter of the Rat

Cited by 43 publications

References 22 publications

Sodium/iodide symporter: a key transport system in thyroid cancer cell metabolism

Sodium/iodide symporter: a key transport system in thyroid cancer cell metabolism

Cloning of the mouse sodium iodide symporter and its expression in the mammary gland and other tissues

Imaging of metastatic pulmonary tumors following NIS gene transfer using single photon emission computed tomography

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