scholarly journals Monoclonal antibodies against the human sodium iodide symporter: utility for immunocytochemistry of thyroid cancer

1999 ◽  
Vol 163 (3) ◽  
pp. 495-504 ◽  
Author(s):  
MR Castro ◽  
ER Bergert ◽  
TG Beito ◽  
PC Roche ◽  
SC Ziesmer ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Fusion Protein ◽  
Sodium Iodide ◽  
Cell Cancer ◽  
Thyroid Tissue ◽  
Follicular Epithelium ◽  
Sodium Iodide Symporter ◽  
Major Band ◽  
Iodide Transport ◽  
And Function

The recent cloning of the thyroidal protein that is responsible for iodide transport, the sodium iodide symporter (hNIS), has made possible studies designed to characterize its structure, function and expression in thyroidal tissues. Using a mannose binding protein (MBP)-hNIS fusion protein as antigen, we have developed mouse monoclonal antibodies against hNIS to utilize as tools in such studies. Twenty-four clones were initially recovered which recognized the MBP-hNIS fusion protein, but only two of them were specific for hNIS while the others recognized MBP alone. Both antibodies were found to be immunoglobulin G (IgG) 1kappa (kappa). The specificity of antibodies was tested by Western blotting using membranes prepared from COS-7 cells transiently transfected with the pcDNA3 plasmid containing the full-length hNIS cDNA, or cells transfected with the pcDNA3 vector. A major band with a molecular weight (MW) of approximately 97 kDa, and several minor bands with MW of approximately 160 kDa, approximately 68 kDa, approximately 30 kDa and approximately 15 kDa, were detected specifically in the hNIS-transfected cells. After enzymatic deglycosylation, the major band was present at 68 kDa, as expected based upon the amino acid sequence of hNIS. Immunohistochemistry was performed with several different types of thyroid tissue and non-thyroidal tissues, using the monoclonal antibodies. Strong immunostaining was observed in Graves' tissue, with intermediate staining in papillary and follicular thyroid cancers and an absence of staining in Hurthle cell cancer. The staining was specific for the follicular epithelium and was concentrated in the basolateral portion of the cell membrane. These monoclonal hNIS antibodies should prove useful in the characterization of NIS expression in benign and malignant thyroid tissue and in studies characterizing its structure and function.

scholarly journals The importance of sodium/iodide symporter (NIS) for thyroid cancer management

2007 ◽  
Vol 51 (5) ◽  
pp. 672-682 ◽  
Author(s):  
Denise P. Carvalho ◽  
Andrea C.F. Ferreira
Keyword(s):  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Therapeutic Tool ◽  
Iodide Transport ◽  
Cancer Management ◽  
Thyroid Hormone Biosynthesis ◽  
Nis Gene ◽  
Hormone Biosynthesis ◽  
Tumoral Cells

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.

scholarly journals Decreased Expression of Thyroglobulin and Sodium Iodide Symporter Genes in Hashimoto’s Thyroiditis

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Anna Popławska-Kita ◽  
Beata Telejko ◽  
Katarzyna Siewko ◽  
Maria Kościuszko-Zdrodowska ◽  
Natalia Wawrusewicz-Kurylonek ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Hashimoto’S Thyroiditis ◽  
Sodium Iodide ◽  
Interleukin 1 ◽  
Thyroid Volume ◽  
Needle Aspiration ◽  
Hashimoto's Thyroiditis ◽  
Sodium Iodide Symporter ◽  
Thyroid Cells ◽  
Iodide Transport

Aim. The aim of the study was to compare the expression of sodium iodide symporter (NIS), thyroglobulin (Tg), tumor necrosis factor-α(TNFα), and interleukin-1βgenes in patients with Hashimoto’s thyroiditis (HT) and healthy individuals.Subjects and Methods.Thyroid cells were obtained from 39 patients with HT and 15 controls by an ultrasound guided fine needle aspiration biopsy.Results. The patients with HT had lower Tg and NIS mRNA (P=0.002andP=0.001, resp.), as well as higher TNFαmRNA expression (P=0.049) than the controls. In the HT group Tg mRNA expression correlated positively with NIS mRNA expression (R=0.739,P=0.0001) and thyroid volume (R=0.465,P=0.0005), as well as negatively with TNFαmRNA expression (R=-0.490,P=0.001) and anti-peroxidase antibodies (TPOAb) level (R=-0.482,P=0.0002), whereas NIS mRNA expression correlated positively with thyroid volume (R=0.319,P=0.02), as well as negatively with TNFαmRNA expression (R=-0.529,P=0.0006) and TPOAb level (R=-0.422,P=0.001).Conclusions.Our results suggest that decreased Tg and NIS expression in thyroid cells may result in reduced active iodide transport and reduced thyroid volume in patients with HT.

scholarly journals Regulation of the sodium iodide symporter by iodide in FRTL-5 cells

2001 ◽  
pp. 139-144 ◽  
Author(s):  
PH Eng ◽  
GR Cardona ◽  
MC Previti ◽  
WW Chin ◽  
LE Braverman
Keyword(s):  
Sodium Iodide ◽  
Cell Model ◽  
High Plasma ◽  
Northern Analysis ◽  
Thyroid Cell ◽  
Transcriptional Level ◽  
Sodium Iodide Symporter ◽  
Iodide Transport ◽  
Excess Iodide

OBJECTIVE: The acute decrease in iodide organification in the thyroid in response to excess iodide is termed the acute Wolff-Chaikoff effect and normal organification resumes in spite of continued high plasma iodide concentrations (escape from the acute Wolff-Chaikoff effect). We have recently reported that large doses of iodide given to rats chronically decrease the sodium/iodide symporter (NIS) mRNA and protein, suggesting that escape is due to a decrease in NIS and subsequent iodide transport. We have now studied the effect of excess iodide on NIS in FRTL-5 cells to further explore the mechanisms whereby excess iodide decreases NIS. DESIGN: FRTL-5 cells were employed and were incubated in the presence or absence of various concentrations of iodide. NIS mRNA and protein and the turnover of NIS were assessed. METHODS: NIS mRNA was measured by Northern analysis, NIS protein by Western analysis and NIS turnover by pulse-chase labeling experiments. RESULTS: Iodide (10(-) mol/l) had no effect on NIS mRNA in FRTL-5 cells at 24 and 48 h compared with cells cultured in the absence of iodide. However, excess iodide decreased NIS protein by 50% of control values at 24 h and by 70% at 48 h. This effect of iodide was dose dependent. Pulse-chase experiments demonstrated that there was no effect of iodide on new NIS protein synthesis and that the turnover of NIS protein in the presence of iodide was 27% faster than in the absence of added iodide. CONCLUSIONS: Excess iodide does not decrease NIS mRNA in FRTL-5 cells but does decrease NIS protein, suggesting that in this in vitro thyroid cell model iodide modulates NIS, at least in part, at a post-transcriptional level. This iodide-induced decrease in NIS protein appears to be due, at least partially, to an increase in NIS protein turnover.

scholarly journals Differentiated thyroid cancer: Growth factors, oncogenes and environmental influences

2003 ◽  
Vol 11 (3) ◽  
pp. 171-172
Author(s):  
Ivan Paunovic
Keyword(s):  
Thyroid Cancer ◽  
Growth Factors ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Sodium Iodide ◽  
Thyroid Tissue ◽  
Suppressor Gene ◽  
Differentiated Thyroid Carcinoma ◽  
Sodium Iodide Symporter ◽  
Normal Thyroid Tissue

The present data of growth factors, oncogenes, tumor-suppressor-genes and environmental factors can be summarized in thus: thyrotropin, growth factors and other hormones do increase thyrocyte growth and specific mutations of growth factor receptors (thyrotropin receptor [TSH-R], alpha subunit of hetero-trimeric transducer protein [GSP]) cause autonomously functioning thyroid tissue and differentiated thyroid carcinoma. In the thyroid, as in other organs, genes that are found to be differentially expressed between normal thyroid tissue and thyroid carcinomas can be used as targets for molecular-based diagnosis and therapy. Deregulation of tumor suppressor gene p53, however, parallels dedifferentiation of papillary and follicular thyroid cancer but has been found in few cases only. Iodide inhibiting thyrocyte growth will have to be investigated more intensively after sodium-iodide-symporter (NIS) has been cloned, and studies may now be available that could lead to form of conservative treatment in especially dedifferentiated thyroid cancer.

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

2001 ◽  
Vol 170 (1) ◽  
pp. 185-196 ◽  
Author(s):  
B Perron ◽  
AM Rodriguez ◽  
G Leblanc ◽  
T Pourcher
Keyword(s):  
Mammary Gland ◽  
Mammalian Cells ◽  
Sodium Iodide ◽  
Distribution Analysis ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Reading Frame ◽  
Hormone Synthesis ◽  
Iodide Transport ◽  
Lactating Mammary Gland

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.

scholarly journals Congenital Hypothyroidism Caused by a PAX8 Gene Mutation Manifested as Sodium/Iodide Symporter Gene Defect

2010 ◽  
Vol 2010 ◽  
pp. 1-3 ◽  
Author(s):  
Wakako Jo ◽  
Katsura Ishizu ◽  
Kenji Fujieda ◽  
Toshihiro Tajima
Keyword(s):  
Thyroid Gland ◽  
Congenital Hypothyroidism ◽  
Sodium Iodide ◽  
Present Report ◽  
Sodium Iodide Symporter ◽  
Loss Of Function ◽  
Laboratory Findings ◽  
Iodide Transport ◽  
Transport Defect ◽  
Pax8 Gene

Loss-of-function mutations of the PAX8 gene are considered to mainly cause congenital hypothyroidism (CH) due to thyroid hypoplasia. However, some patients with PAX8 mutation have demonstrated a normal-sized thyroid gland. Here we report a CH patient caused by a PAX8 mutation, which manifested as iodide transport defect (ITD). Hypothyroidism was detected by neonatal screening and L-thyroxine replacement was started immediately. Although I scintigraphy at 5 years of age showed that the thyroid gland was in the normal position and of small size, his iodide trapping was low. The ratio of the saliva/plasma radioactive iodide was low. He did not have goiter; however laboratory findings suggested that he had partial ITD. Gene analyses showed that the sodium/iodide symporter (NIS) gene was normal; instead, a mutation in the PAX8 gene causing R31H substitution was identified. The present report demonstrates that individuals with defective PAX8 can have partial ITD, and thus genetic analysis is useful for differential diagnosis.

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