Disease relevance of SLC5A5

• In 6 thyroid carcinoma patients, 131I uptake was studied in vivo; NIS expression was low in all samples; 3 patients with normal Glut-1 gene expression had 131I uptake in metastases, whereas the other 3 patients with increased Glut-1 gene expression had no detectable 131I uptake [1].
• NIS expression was decreased in 40 of 43 thyroid carcinomas (10- to 1200-fold) and in 20 of 24 cold adenomas (2- to 700-fold); it was increased in toxic adenomas and Graves' thyroid tissues (up to 140-fold) [1].
• The increased expression of NIS may thus contribute to the development of Graves' disease [2].
• Several studies suggest that the sodium-iodide symporter (NIS) may represent a major autoantigen in autoimmune diseases of the thyroid [3].
• The aim of the present paper was to investigate the importance of autoantibodies to human NIS (hNIS-Ab) in patients suffering from Hashimoto's thyroiditis (HT) and Graves' disease (GD) [3].

Psychiatry related information on SLC5A5

• Official statistics showed that alcohol consumption in the CCEE/NIS rose from the 1960s to the mid-1980s, and then remained stable or fell in most countries [4].

High impact information on SLC5A5

• NIS plays key roles in thyroid pathophysiology as the route by which iodide reaches the gland for thyroid hormone biosynthesis and as a means for diagnostic scintigraphic imaging and for radioiodide therapy in hyperthyroidism and thyroid cancer [5].
• The Na(+)/I(-) symporter (NIS) is an intrinsic membrane protein that mediates the active transport of iodide into the thyroid and other tissues, such as salivary glands, gastric mucosa, and lactating mammary gland [5].
• The sodium/iodide Symporter (NIS): characterization, regulation, and medical significance [6].
• Most dramatically, the discovery of endogenous NIS expression in more than 80% of human breast cancer samples has raised the possibility that radioiodide may be a valuable novel tool in breast cancer diagnosis and treatment [6].
• The Na(+)/I(-) symporter (NIS) is an integral plasma membrane glycoprotein that mediates active I(-) transport into the thyroid follicular cells, the first step in thyroid hormone biosynthesis [6].

Chemical compound and disease context of SLC5A5

• Kinetics of iodide uptake and efflux in various human thyroid cancer cells by expressing sodium iodide symporter gene via a recombinant adenovirus [7].
• Intraperitoneal injection of potassium iodide resulted in significant tumor volume reduction in NIS/TPO-modified tumor xenografts without apparent adverse effects in SCID mice [8].
• It was shown previously that hNIS mRNA expression is stimulated by retinoic acid (RA) in human follicular thyroid carcinoma cell lines FTC-133 and FTC-238, and patients with thyroid carcinomas lacking iodide uptake respond to RA treatment with increased radioiodide transport [9].
• BACKGROUND: The sodium/iodide symporter (NIS) is a membrane glycoprotein that mediates active 131I uptake during the treatment of cancer of the thyroid gland and extrathyroidal tissues [10].
• Androgen-dependent prostate cancer cell lines (LNCaP) and non-prostate origin tumor cell lines (SNU449, MCF-7, HCT116, OVCAR-3, and Panc-1) were infected with the viral constructs, and perchlorate-sensitive (125)I uptake and NIS protein expression were measured [11].

Biological context of SLC5A5

• Our data indicate that hNIS is not a major antigen in autoimmune thyroid disease, as it is the target of humoral autoimmunity in only a few patients with GD and HT [3].
• The expression of the NIS gene is up-regulated by TSH through the cAMP pathway and the characterization of the promoter region of the rat NIS gene revealed the existence of a degenerate cAMP response element (CRE) sequence [12].
• Increased intracellular iodide concentration is mediated by IgG, which activates the upstream enhancer of the sodium/iodide symporter (NIS) [13].
• The molecular processes explaining the principles of radioiodine treatment remained unresolved until the genetics and the functionality of the human sodium-iodide symporter (hNIS) were recently identified [13].
• No significant difference between the two genotypes was found for Pax8, sodium iodide symporter, and iodothyronine deiodinase 1 [14].

Anatomical context of SLC5A5

• The Na+/I- symporter (NIS) is important in hormone synthesis in the thyroid gland [2].
• OBJECTIVE: Reduced expression or defective targeting of the sodium/iodide symporter (NIS) to the cell membrane in thyroid tumours has been reported [12].
• No correlation was found in hNIS mRNA expression between primary and lymph node metastatic tissues [15].
• 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 [16].
• We have studied the role of flavonoids on the iodide transport and the growth of the human follicular thyroid cancer cell line (FTC133) which was stably transfected with the human Na(+)/I(-) symporter (hNIS) [17].

Associations of SLC5A5 with chemical compounds

• The sodium iodide symporter (NIS) is a plasma membrane protein that is responsible for iodide transport into thyroid cells [15].
• We performed an in vitro study specifically aimed at examining the effects of lithium on the sodium iodide symporter (NIS) [18].
• Kaempferol, apigenin, luteolin and F21388 decreased NIS mRNA expression after 15, 29 and 48 h; after 96 h NIS mRNA returned to normal [17].
• NIS also mediates active I(-) transport in other tissues, including salivary glands, gastric mucosa, and lactating mammary gland, in which it translocates I(-) into the milk for thyroid hormone biosynthesis by the nursing newborn [6].
• Inhibition of the p38-MAPK pathway with SB203580 partially but significantly, attenuates cAMP- and TSH-induced expression of the sodium iodide symporter in FRTL-5 cells [19].
• Iodide inhibited NIS mRNA and membrane protein expression as well as (125)I uptake, which were paralleled by decreased betahCG mRNA expression and protein secretion [20].

Physical interactions of SLC5A5

• BACKGROUND: Sodium/iodide symporter (NIS) is a key protein in iodide transport by thyroid cells and this activity is a prerequisite for effective radioiodide treatment of thyroid cancer [21].

Regulatory relationships of SLC5A5

• Thyroid-stimulating hormone receptor expressing cells also expressed the sodium iodide symporter and thyroglobulin genes [22].
• Conversely, overexpression of the HDAC 1 enzyme inhibited basal activity of the NIS promoter [23].
• Thus, TPO could be used as a therapeutic strategy to enhance the NIS-based radioiodide concentrator gene therapy for locally advanced lung cancer [24].
• We show that expression of NIS and PDS are differentially regulated by Tg concentration and exposure time [25].
• Establishment of a human hepatocellular carcinoma cell line highly expressing sodium iodide symporter for radionuclide gene therapy [26].

Other interactions of SLC5A5

• Higher tumor stages (stages >I vs stage I) were associated with lower expression of NIS (P = 0.03) and TPO (P < 0.01) [1].
• The correlation of mRNA levels between hNIS and thyroid-specific genes, thyrotropin (TSH) receptor, and thyroglobulin (Tg), were also investigated [15].
• CONCLUSIONS: Our results have indicated for the first time that reduced levels of CREB expression are a feature of thyroid carcinomas, and confirm that different factors are likely to modulate NIS expression [12].
• The level of hNIS mRNA was correlated with the levels of TSH receptor (r = 0.449, p < 0.05), but not with Tg mRNA [15].
• This is the first demonstration of both extensive and local homologies between one thyroid autoantigen (NIS) and microbiological proteins [27].

Analytical, diagnostic and therapeutic context of SLC5A5

• Northern blot analysis revealed that incubation of these cells with TSH or forskolin for 24 h increased the abundance of NIS messenger ribonucleic acid (mRNA) 2.3- and 2.5-fold, respectively [2].
• The levels of hNIS mRNA in lymph node metastatic tissues were evaluated by RT-PCR [15].
• Our results significantly indicate that co-expression of TPO in NIS transfected cells mediates iodination on the one hand but on the other hand does not contribute to augmentation of a putative NIS-based radioiodide concentrator gene therapy [28].
• Consequently, the hNIS protein could be readily detected by Western blot analysis 48-h post-infection at 10 infectious virus particles per cell [7].
• Antipeptide antibodies raised against the carboxyl-terminal region of the human sodium/iodide (Na+/I-) symporter (hNIS) were used to investigate by immunohistochemistry the presence and distribution of the hNIS protein in normal thyroid tissues, in some pathological nonneoplastic thyroid tissues, and in different histotypes of thyroid neoplasms [29].

References