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DOI: 10.1055/s-2001-11013
© Johann Ambrosius Barth
Sodium/iodide symporter mRNA expression in cold thyroid nodules
Publication History
Publication Date:
31 December 2001 (online)
Summary:
Clinical and experimental data suggest a low thyroid hormone synthesis in cold thyroid nodules (CTN). Therefore, the Na+/I--symporter (NIS) as the first step in the thyroid hormone synthesis could be a possible candidate gene in the pathogenesis of CTNs. A reduction of NIS transcripts in CTNs compared to samples of normal thyroid tissues with large inter-individual variations ranging from 2- to 700-fold reductions was observed with real-time RT-PCR. Therefore, the aim of our investigations was to perform an intra-individual comparison of NIS expression in CTNs. Moreover, we used direct detection of NIS mRNA by RNase protection assay (RPA). We investigated 14 patients with one CTN for NIS mRNA expression. NIS mRNA transcripts from nodule and surrounding tissue were examined by RPA. A significantly reduced NIS expression was detected in 86% of the CTNs compared to their corresponding surrounding tissue. The level of NIS expression was decreased to more than 65% in 10 CTNs (72% of the nodules). Two of the 14 nodules showed a decrease of NIS mRNA expression of 42%, and 32%, while no significant differences could be detected in 2 cold nodules. Compared to other studies the intra-individual comparison of NIS mRNA expression revealed a much lower variation of reduced NIS expression in CTNs. Further studies should try to identify molecular factors like post-transcriptional modifications or alterations in iodide organification which are likely to be involved in the pathogenesis of CTNs.
Key words:
Na+/I- symporter - cold thyroid nodule - mRNA-expression
References
- 1 Ajjan R A, Kamaruddin N A, Crisp M, Watson P F, Ludgate M, Weetman A P. Regulation and tissue distribution of the human sodium iodide symporter gene. Clin Endocrinol (Oxf.). 49 517-523 1998;
- 2 Arturi F, Russo D, Schlumberger M. et al. . Iodide symporter gene expression in human thyroid tumors. J Clin Endocrinol Metab. 83 2493-2496 1998;
- 3 Dai G, Levy O, Carrasco N. Cloning and characterization of the thyroid iodide transporter. Nature. 379 458-460 1996;
- 4 De Groot L. Lack of iodide trapping in “cold” thyroid nodules. Acta Endocrinol (Panam). 1 27-31 1970;
- 5 Demeester-Mirkine N, Van Sande J, Corvilain J, Dumont J E. Benign thyroid nodule with normal iodide trap and defective organification. J Clin Endocrinol Metab. 41 1169-1171 1975;
- 6 Endo T, Kaneshige M, Nakazato M, Ohmori M, Harii N, Onaya T. Thyroid transcription factor-1 activates the promoter activity of rat thyroid Na+/I- symporter gene. Mol Endocrinol. 11 1747-1755 1997;
- 7 Eszlinger M. EGF and TGF-β1 expression in toxic thyroid nodules and cold thyroid nodules. 26th Annual Meeting of the European Thyroid Association. J Endocrinol Invest. 22 24 1999;
- 8 Field J B, Larsen P R, Yamashita K, Mashiter K, Dekker A. Demonstration of iodide transport defect but normal iodide organification in nonfunctioning nodules of human thyroid glands. J Clin Invest. 52 2404-2410 1973;
- 9 Hedinger C, Williams E, Sobin L. Histological typing of thyroid tumors. In: International histological classification of tumors. Berlin Heidelberg New York: Springer Verlag 8: 1431-1432 1988
- 10 Joba W, Spitzweg C, Schriever K, Heufelder A E. Analysis of human sodium/iodide symporter, thyroid transcription factor- 1, and paired-box-protein-8 gene expression in benign thyroid diseases. Thyroid. 9 455-466 1999;
- 11 Lazar V, Bidart J M, Caillou B. et al. . 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 1999;
- 12 Levy O, De la Vieja A, Carrasco N. The Na+/I- symporter (NIS): recent advances. J Bioenerg Biomembr. 30 195-206 1998;
- 13 Neumann S, Reske A, Schuchardt K, Paschke R. Decreased NIS expression and lack of somatic NIS mutations in cold thyroid nodules. Experimental and Clinical Endocrinology and Diabetes. Suppl. 1, 108: 52 2000
- 14 Saito T, Endo T, Kawaguchi A. et al. . Increased expression of the sodium/iodide symporter in papillary thyroid carcinomas. J Clin Invest. 101 1296-1300 1998;
- 15 Schurch M, Peter H J, Gerber H, Studer H. Cold follicles in a multinodular human goiter arise partly from a failing iodide pump and partly from deficient iodine organification. J Clin Endocrinol Metab. 71 1224-1229 1990;
- 16 Smanik P A, Liu Q, Furminger T L. et al. . Cloning of the human sodium iodide symporter. Biochem Biophys Res Commun. 226 339-345 1996;
- 17 Venkataraman G M, Yatin M, Ain K B. Cloning of the human sodium-iodide symporter promoter and characterization in a differentiated human thyroid cell line, KAT-50. Thyroid. 8 63-69 1998;
Ralf PaschkeM.D.
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