Skip to main content

Sodium Iodide Symporter in Thyroid Carcinoma

  • Chapter
  • First Online:
Therapeutic Nuclear Medicine

Part of the book series: Medical Radiology ((Med Radiol Radiat Oncol))

  • 2645 Accesses

Abstract

Thyroid iodide uptake is essential for the clinical application of radioiodine in patients with well-differentiated thyroid carcinoma. Iodide uptake occurs across the plasma membranes of thyroid follicular cells and cancer cells via an active transporter process mediated by sodium iodide symporter (NIS). The cloning of the NIS gene enabled the molecular mechanisms underlying iodide transport to be better characterized, and thus, opened the way to the expansion of its role in thyroid carcinoma. Thyroid-stimulating hormone (TSH) is the principal regulator of iodide uptake, although many other factors, including insulin, insulin-like growth factor I, epidermal growth factor, and iodide itself, also influence iodide uptake by the thyroid gland. Human NIS expression may be increased, decreased, or absent in well-differentiated thyroid cancer. However, the reason for reduced iodide uptake in well-differentiated thyroid carcinoma is not solely due to lower NIS expression, and probably depends on a complex combination of regulatory changes that ultimately affect NIS expression, targeting, or activation. Nevertheless, reduced functional levels of NIS on cell membranes do account for the reduced iodide uptake observed in thyroid carcinoma. Furthermore, thyroid cancer tissues expressing NIS take up more I-131 than those not expressing NIS, and these tumors subsequently show a higher rate of response to radioiodine therapy. Accordingly, NIS appears to have the potential to expand the role of nuclear medicine in the management of thyroid carcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ajjan RA, Watson FF, Findlay C et al (1998a) The sodium iodide symporter gene and its regulation by cytokines found in autoimmunity. J Endocrinol 158:351–358

    Article  CAS  PubMed  Google Scholar 

  • Ajjan RA, Kamaruddin NA, Crisp M, Watson PF, Ludgate M, Weetman AP (1998b) Regulation and tissue distribution of the human sodium iodide symporter gene. Clin Endocrinol 49:517–523

    Article  CAS  Google Scholar 

  • Arturi F, Russo D, Schlumberger M et al (1998) Iodide symporter gene expression in human thyroid tumors. J Clin Endocrinol Metab 83:2493–2496

    CAS  PubMed  Google Scholar 

  • Baumann E (1986) Uber den Jodgehalt der Schilddrusen von Mechen und tieren. Hoppe-Seyler’s Zeitsehrift fur Physiologische Chemie 22:1–17

    Google Scholar 

  • Caillou B, Troalen F, Baudin E et al (1998) Na+/I-symporter distribution in human thyroid tissues: an immunohistochemical study. J Clin Endocrinol Metab 83:4102–4106

    CAS  PubMed  Google Scholar 

  • Chung J-K (2002) Sodium/iodide symporter: its role in nuclear medicine. J Nucl Med 43:1188–1200

    CAS  PubMed  Google Scholar 

  • Chung J-K, So Y, Lee JS et al (1999) Value of FDG PET in papillary thyroid carcinoma with negative 131I whole-body scan. J Nucl Med 40:986–992

    CAS  PubMed  Google Scholar 

  • Dai G, Levy O, Carrasco N (1996) Cloning and characterization of the thyroid iodide transporter. Nature 379:458–460

    Article  CAS  PubMed  Google Scholar 

  • Dohan O, Baloch Z, Banrevi Z, Livolsi V, Carrasco N (2001) Predominant intracellular overexpression of the Na+/I-symporter (NIS) in a large sampling of thyroid cancer cases. J Clin Endocrinol Metab 86:2697–2700

    CAS  PubMed  Google Scholar 

  • Dohan O, Ginter CS, Carrasco N (2005) Role of the NIS (Na+/I-symporter) carboxy terminus in iodide transport. Thyroid 15:S48

    Google Scholar 

  • Endo T, Kaneshige M, Nakazato M et al (1997) Thyroid transcription factor-1 activates the promoter rat Na+/I-symporter gene. Mol Endocrinol 11:1747–11755

    CAS  PubMed  Google Scholar 

  • Eng PH, Cardona GR, Fang SL et al (1999) Escape from the acute Wolff-Chaikoff effect is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein. Endocrinology 140:3401–3410

    Google Scholar 

  • Eskandari S, Loo DDF, Dai G, Levy O, Wright EM, Carrasco N (1997) Thyroid Na+/I-symporter. J Biol Chem 272:27230–27238

    Article  CAS  PubMed  Google Scholar 

  • Filetti S, Bidart J-M, Arturi F, Caillou B, Russo D, Schlumberger M (1999) Sodium/iodide symporter: a key transport system in thyroid cancer cell metabolism. Eur J Endocrinol 141:443–457

    Article  CAS  PubMed  Google Scholar 

  • Fugazzola L, Puxeddu E, Avenia N et al (2006) Correlation between B-RAFV600E mutation and clinico-pathologic parameters in papillary thyroid carcinoma: data from a multicentric Italian study and review of the literature. Endocr Relat Cancer 13:455–464

    Article  CAS  PubMed  Google Scholar 

  • Furlanetto TW, Nguyen LO, Jameson JL (1999) Estradiol increases proliferation and down-regulates the sodium/iodide symporter gene in FRTL-5cells. Endocrinology 140:5705–5711

    CAS  PubMed  Google Scholar 

  • Jung YH, Hah JH, Sung M-W et al (2009) Reciprocal immunohistochemical expression of sodium/iodide symporter and hexokinase I in primary thyroid tumors with synchronous cervical metastasis. Laryngoscope 119:541–548

    Article  CAS  PubMed  Google Scholar 

  • Kogai T, Endo T, Saito T et al (2000a) Induction of follicular formation in long-term cultured normal human thyroid cells treated with thyrotropin stimulates iodide uptake but not sodium/iodide symporter messenger RNA and protein expression. J Endocrinol 167:125–135

    Article  CAS  PubMed  Google Scholar 

  • Kogai T, Schultz JJ, Johnson LS, Huang M, Brent GA (2000b) Retinoic acid induces sodium/iodide symporter gene expression and radioiodide uptake in the MCF-7 breast cancer cell line. Proc Natl Acad Sci U S A 97:8519–8524

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kogai T, Hershman JM, Motomura K, Endo T, Onaya T, Brent GA (2001) Differential regulation of the human sodium/iodide symporter gene promoter in papillary thyroid carcinoma cell lines and normal thyroid cells. Endocrinology 142:3369–3379

    Article  CAS  PubMed  Google Scholar 

  • Kogai T, Taki K, Brent GA (2006) Enhancement of sodium/iodide symporter expression in thyroid and breast cancer. Endocr Relat Cancer 13:797–826

    Article  CAS  PubMed  Google Scholar 

  • Lazar V, Bidart J-M, Caillou B et al (1999) Expression of the Na/I symporter gene in human thyroid tumors: a comparison study with other thyroid-specific genes. J Clin Endocrinol Metab 84:3228–3234

    CAS  PubMed  Google Scholar 

  • Lee BW, Lee DS Moon DH et al (1990) Comparison of I-131 diagnostic scan and therapeutic scan in thyroid carcinoma. Nucl Med Mol Imaging 24:80–86

    Google Scholar 

  • Levy O, De la Vieja A, Carrasco N (1998) The Na+/I-symporter (NIS): recent advances. J Bioenerg Biomembr 30:195–206

    Article  CAS  PubMed  Google Scholar 

  • Magliano MP, Lauro RD, Zannini M (2000) Pax8 has a key role in thyroid cell differentiation. Proc Natl Acad Sci U S A 97:13144–13149

    Article  Google Scholar 

  • Min J-J, Chung J-K, Lee YJ et al (2001) Relationship between expression of the sodium/iodide symporter and I-131 uptake in recurrent lesions of differentiated thyroid carcinoma. Eur J Nucl Med 28:639–645

    Article  CAS  Google Scholar 

  • Ohmori M, Endo T, Harii N, Onaya T (1998) A novel thyroid transcription factor is essential for thyrotropin-induced up-regulation of Na+/I-symporter gene expression. Mol Endocrinol 12:727–736

    CAS  PubMed  Google Scholar 

  • Park HJ, Kim JY, Park KY, Gong G, Hong SJ, Ahn IM (2000) Expressions of human sodium iodide symporter mRNA in primary and metastatic papillary thyroid carcinoma. Thyroid 10:211–217

    Article  CAS  PubMed  Google Scholar 

  • Pekari AE, Hersam JM (1998) Tumor necrosis factor, ceremide, transforming growth factor-beta1 and aging reduce Na+/I-symporter messenger ribonucleic acid levels in FRTL-5 cells. Endocirnology 139:7033712

    Google Scholar 

  • Riedel C, Levy O, Carrasco N (2001) Post-transcriptional regulation of sodium/iodide symporter by thyrotropin. J Biol Chem 276:21458–21463

    Article  CAS  PubMed  Google Scholar 

  • Riesco-Eizaguirre G, Santisteban P (2006) A perspective view of sodium iodide symporter research and its clinical implications. Eur J Endocrinol 155:495–512

    Article  CAS  PubMed  Google Scholar 

  • Riesco-Eizaguirre G, Gutierrez-Martinez P, Garcia’-Cabezas M, Nistal M, Santisteban P (2006) The oncogene BRAFV600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na/I targeting to the membrane. Endocr Relat Cancer 13:257–269

    Google Scholar 

  • Riggs DS (1952) Quantitative aspects of iodine metabolism in man. Pharmacol Rev 4:284–370

    CAS  PubMed  Google Scholar 

  • Saito T, Endo T, Kawaguchi A et al (1998) Increased expression of the sodium/iodide symporter in papillary thyroid carcinomas. J Clin Invest 101:1296–1300

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Shen DHY, Kloos RT, Mazaferri EL, Jhiang SM (2001) Sodium iodide symporter in health and disease. Thyroid 11:415–425

    Article  CAS  PubMed  Google Scholar 

  • Smanik PA, Liu Q, Furminger TL et al (1996) Cloning of the human sodium iodide symporter. Biochem Biophys Res Commun 226:339–345

    Article  CAS  PubMed  Google Scholar 

  • Spitzweg C, Heufelder AE (1998) The sodium iodide symporter: its emerging relevance to clinical thyroidology. Eur J Endocrinol 138:374–375

    Article  CAS  PubMed  Google Scholar 

  • Spitzweg C, Joba W, Eisenmenger W, Heufelder AE (1998) Analysis of human sodium iodide symporter gene expression in extrathyroidal tissues and cloning of its complementary deoxyribonucleic acids from salivary gland, mammary gland, and gastric mucosa. J Clin Endocrinol Metab 83:1746–1751

    Article  CAS  PubMed  Google Scholar 

  • Tazebay UH, Wapnir IL, Levy O et al (2000) The mammary gland iodide transporter is expressed during lactation and in breast cancer. Nat Med 6:871–878

    Article  CAS  PubMed  Google Scholar 

  • Trapasso F, Iuliano R, Chiefari E et al (1999) Iodide symporter gene expression in normal and transformed rat thyroid cells. Eur J Endocrinol 140:447–451

    Article  CAS  PubMed  Google Scholar 

  • Trouttet-Masson S, Selmi-Ruby S, Bernier-Valentin F et al (2004) Evidence for transcriptional and posttranscriptional alterations of the sodium/iodide symporter expression in hypofunctioning benign and malignant thyroid tumors. Am J Pathol 165:25–34

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Trovisco V, Vieira de Castro I, Soares P et al (2004) BRAF mutations are associated with some histological types of papillary thyroid carcinoma. J Pathol 202:247–251

    Google Scholar 

  • Uyttersprot N, Pelgrims N, Carrasco N et al (1997) Moderate doses of iodide in vivo inhibit cell proliferation and expression of thyroid peroxidase and the Na+/I-symporter mRNAs in dog thyroid. Mol Cell Endocrinol 131:195–203

    Article  CAS  PubMed  Google Scholar 

  • Vadyssirisack DD, Chen E, Zhang Z et al (2007) Identification of in vivo phosphorylation sites and their functional significance in the sodium iodide symporter. J Biol Chem 282:36820–36828

    Article  Google Scholar 

  • Wapnir IL, van de Rijn M, Nowels K et al (2003) Immunohistochemical profile of the sodium/iodide symporter in thyroid, breast and other carcinomas using high density tissue microarrays and conventional sections. J Clin Endocrinol Metab 88:1880–1888

    Article  CAS  PubMed  Google Scholar 

  • Weiss SJ, Philip NJ, Ambesi-Impiombato FS, Grollman EF (1984) Thyrotropin-stimulated iodide transport mediated by adenosine 3′,5′-monophosphate and dependent on protein synthesis. Endocrinology 114:1099–1107

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to June-Key Chung .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Chung, JK. (2012). Sodium Iodide Symporter in Thyroid Carcinoma. In: Baum, R. (eds) Therapeutic Nuclear Medicine. Medical Radiology(). Springer, Berlin, Heidelberg. https://doi.org/10.1007/174_2012_731

Download citation

  • DOI: https://doi.org/10.1007/174_2012_731

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-36718-5

  • Online ISBN: 978-3-540-36719-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics