This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Arturi, F. Articles by Filetti, S. Search for Related Content PubMed PubMed Citation Articles by Arturi, F. Articles by Filetti, S.

Iodide Symporter Gene Expression in Human Thyroid Tumors¹

Cattedra di Endocrinologia, Dipartimento di Medicina Sperimentale e Clinica (F.A., E.C., S.F.), and Cattedra di Farmacologia, Facoltà di Farmacia (D.R.), Università di Catanzaro, 88100 Catanzaro; and Oncologia Sperimentale, Istituto Nazionale Tumori (P.V.), Milan, Italy; and Institut de Recherches Scientifiques sur le Cancer, Centre National de Recherches Scientifiques (J.-A.D., R.W., H.G.S.), 94802 Villejuif; and Institut Gustave Roussy (M.S., B.C.), 94805 Villejuif, France

Address all correspondence and requests for reprints to: Sebastiano Filetti, M.D., Cattedra di Endocrinologia, Dipartimento di Medicina Sperimentale e Clinica, Via T. Campanella, 88100 Catanzaro, Italy. E-mail: filetti{at}tin.it

Expression of the Na⁺/I^- symporter (NIS) gene was investigated by RT-PCR in a selected series of 26 primary thyroid carcinomas (19 papillary, 5 follicular, and 2 anaplastic). Fifteen follicular adenomas (11 "cold " and 4 "hot" adenomas) were also studied. Five of 19 papillary thyroid cancer did not express NIS messenger ribonucleic acid (mRNA). In all but 1 follicular cancer, NIS transcript was fully detected. In anaplastic tissue, NIS mRNA was only barely detected in 1 case. All of the follicular thyroid adenomas except 1 expressed the NIS gene. In contrast, all tumors studied excluding the anaplastic histotype fully expressed thyroglobulin and thyroid peroxidase mRNA transcripts. In 2 patients, a lower expression (3- to 5-fold) of NIS mRNA was found in metastasis by dot blot analysis compared with those in both normal and primary neoplastic thyroid tissue. Four of 8 differentiated thyroid cancer patients selected for the presence of metastases with negative posttherapy ¹³¹I total body scan showed the lack of NIS gene expression in their primary cancer. This defect, at least in these cases, is a somatic and intrinsic lesion of the primary cancer cells and is not due to a dedifferentiation process in the metastatic tissue. The early detection of the loss of NIS gene expression in the primary cancer, therefore, may provide useful information for the management of differentiated thyroid cancer patients.

This article has been cited by other articles:

				I. Peyrottes, V. Navarro, A. Ondo-Mendez, D. Marcellin, L. Bellanger, R. Marsault, S. Lindenthal, F. Ettore, J. Darcourt, and T. Pourcher Immunoanalysis indicates that the sodium iodide symporter is not overexpressed in intracellular compartments in thyroid and breast cancers Eur. J. Endocrinol., February 1, 2009; 160(2): 215 - 225. [Abstract] [Full Text] [PDF]

				R.-S. LIU, Y.-J. HSIEH, C.-C. KE, F.-D. CHEN, L. HWU, F.-H. WANG, J.-J. HWANG, C.-W. CHI, C.-H. LEE, and S.-H. YEH Specific Activation of Sodium Iodide Symporter Gene in Hepatoma Using Alpha-fetoprotein Promoter Combined with Hepatitis B Virus Enhancer (EIIAPA) Anticancer Res, January 1, 2009; 29(1): 211 - 221. [Abstract] [Full Text] [PDF]

				A. K. M. B. Sodre, I. G. S. Rubio, A. L. R. Galrao, M. Knobel, E. K. Tomimori, V. A. F. Alves, C. T. Kanamura, C. A. Buchpiguel, T. Watanabe, C. U. M. Friguglietti, et al. Association of Low Sodium-Iodide Symporter Messenger Ribonucleic Acid Expression in Malignant Thyroid Nodules with Increased Intracellular Protein Staining J. Clin. Endocrinol. Metab., October 1, 2008; 93(10): 4141 - 4145. [Abstract] [Full Text] [PDF]

				R. B T Verkooijen, F. A Verburg, J. W van Isselt, C. J M Lips, J. W Smit, and M. P M Stokkel The success rate of I-131 ablation in differentiated thyroid cancer: comparison of uptake-related and fixed-dose strategies Eur. J. Endocrinol., September 1, 2008; 159(3): 301 - 307. [Abstract] [Full Text] [PDF]

				C. Romei, R. Ciampi, P. Faviana, L. Agate, E. Molinaro, V. Bottici, F. Basolo, P. Miccoli, F. Pacini, A. Pinchera, et al. BRAFV600E mutation, but not RET/PTC rearrangements, is correlated with a lower expression of both thyroperoxidase and sodium iodide symporter genes in papillary thyroid cancer Endocr. Relat. Cancer, June 1, 2008; 15(2): 511 - 520. [Abstract] [Full Text] [PDF]

				T. Takano, Y. Ito, F. Matsuzuka, A. Miya, K. Kobayashi, H. Yoshida, and A. Miyauchi Expression of Oncofetal Fibronectin mRNA in Thyroid Anaplastic Carcinoma Jpn. J. Clin. Oncol., September 1, 2007; 37(9): 647 - 651. [Abstract] [Full Text] [PDF]

				D. D Vadysirisack, A. Venkateswaran, Z. Zhang, and S. M Jhiang MEK signaling modulates sodium iodide symporter at multiple levels and in a paradoxical manner Endocr. Relat. Cancer, June 1, 2007; 14(2): 421 - 432. [Abstract] [Full Text] [PDF]

				K. Krause, S. Karger, A. Schierhorn, S. Poncin, M.-C. Many, and D. Fuhrer Proteomic Profiling of Cold Thyroid Nodules Endocrinology, April 1, 2007; 148(4): 1754 - 1763. [Abstract] [Full Text] [PDF]

				D. Liu, S. Hu, P. Hou, D. Jiang, S. Condouris, and M. Xing Suppression of BRAF/MEK/MAP Kinase Pathway Restores Expression of Iodide-Metabolizing Genes in Thyroid Cells Expressing the V600E BRAF Mutant Clin. Cancer Res., February 15, 2007; 13(4): 1341 - 1349. [Abstract] [Full Text] [PDF]

				T Kogai, K Taki, and G A Brent Enhancement of sodium/iodide symporter expression in thyroid and breast cancer. Endocr. Relat. Cancer, September 1, 2006; 13(3): 797 - 826. [Abstract] [Full Text] [PDF]

				Y. Y Liu, M. P Stokkel, A. M Pereira, E. P Corssmit, H. A Morreau, J. A Romijn, and J. W A Smit Bexarotene increases uptake of radioiodide in metastases of differentiated thyroid carcinoma. Eur. J. Endocrinol., April 1, 2006; 154(4): 525 - 531. [Abstract] [Full Text] [PDF]

				C. Puppin, F. D'Aurizio, A. V. D'Elia, L. Cesaratto, G. Tell, D. Russo, S. Filetti, E. Ferretti, E. Tosi, T. Mattei, et al. Effects of Histone Acetylation on Sodium Iodide Symporter Promoter and Expression of Thyroid-Specific Transcription Factors Endocrinology, September 1, 2005; 146(9): 3967 - 3974. [Abstract] [Full Text] [PDF]

				F. Arturi, E. Ferretti, I. Presta, T. Mattei, A. Scipioni, D. Scarpelli, R. Bruno, L. Lacroix, E. Tosi, A. Gulino, et al. Regulation of Iodide Uptake and Sodium/Iodide Symporter Expression in the MCF-7 Human Breast Cancer Cell Line J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2321 - 2326. [Abstract] [Full Text] [PDF]

				R. M. Dwyer, E. R. Bergert, M. K. O'Connor, S. J. Gendler, and J. C. Morris In vivo Radioiodide Imaging and Treatment of Breast Cancer Xenografts after MUC1-Driven Expression of the Sodium Iodide Symporter Clin. Cancer Res., February 15, 2005; 11(4): 1483 - 1489. [Abstract] [Full Text] [PDF]

				G. Tell, A. Pines, F. Arturi, L. Cesaratto, E. Adamson, C. Puppin, I. Presta, D. Russo, S. Filetti, and G. Damante Control of Phosphatase and Tensin Homolog (PTEN) Gene Expression in Normal and Neoplastic Thyroid Cells Endocrinology, October 1, 2004; 145(10): 4660 - 4666. [Abstract] [Full Text] [PDF]

				S. Trouttet-Masson, S. Selmi-Ruby, F. Bernier-Valentin, V. Porra, N. Berger-Dutrieux, M. Decaussin, J.-L. Peix, A. Perrin, C. Bournaud, J. Orgiazzi, et al. Evidence for Transcriptional and Posttranscriptional Alterations of the Sodium/Iodide Symporter Expression in Hypofunctioning Benign and Malignant Thyroid Tumors Am. J. Pathol., July 1, 2004; 165(1): 25 - 34. [Abstract] [Full Text] [PDF]

				X. Lin, A. H. Fischer, K.-y. Ryu, J.-y. Cho, T. J. Sferra, R. T. Kloos, E. L. Mazzaferri, and S. M. Jhiang Application of the Cre/loxP System to Enhance Thyroid-Targeted Expression of Sodium/Iodide Symporter J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2344 - 2350. [Abstract] [Full Text] [PDF]

				C. Puppin, A. V. D'Elia, L. Pellizzari, D. Russo, F. Arturi, I. Presta, S. Filetti, C. W. Bogue, L. A. Denson, and G. Damante Thyroid-specific transcription factors control Hex promoter activity Nucleic Acids Res., April 1, 2003; 31(7): 1845 - 1852. [Abstract] [Full Text] [PDF]

				O. Dohan, A. De la Vieja, V. Paroder, C. Riedel, M. Artani, M. Reed, C. S. Ginter, and N. Carrasco The Sodium/Iodide Symporter (NIS): Characterization, Regulation, and Medical Significance Endocr. Rev., February 1, 2003; 24(1): 48 - 77. [Abstract] [Full Text] [PDF]

				T. Kondo, N. Nakamura, K. Suzuki, S.-i. Murata, A. Muramatsu, A. Kawaoi, and R. Katoh Expression of Human Pendrin in Diseased Thyroids J. Histochem. Cytochem., February 1, 2003; 51(2): 167 - 173. [Abstract] [Full Text] [PDF]

				K. Taki, T. Kogai, Y. Kanamoto, J. M. Hershman, and G. A. Brent A Thyroid-Specific Far-Upstream Enhancer in the Human Sodium/Iodide Symporter Gene Requires Pax-8 Binding and Cyclic Adenosine 3',5'-Monophosphate Response Element-Like Sequence Binding Proteins for Full Activity and Is Differentially Regulated in Normal and Thyroid Cancer Cells Mol. Endocrinol., October 1, 2002; 16(10): 2266 - 2282. [Abstract] [Full Text] [PDF]

				J.-K. Chung Sodium Iodide Symporter: Its Role in Nuclear Medicine J. Nucl. Med., September 1, 2002; 43(9): 1188 - 1200. [Abstract] [Full Text] [PDF]

				F. Arturi, L. Lacroix, I. Presta, D. Scarpelli, B. Caillou, M. Schlumberger, D. Russo, J.-M. Bidart, and S. Filetti Regulation by Human Chorionic Gonadotropin of Sodium/Iodide Symporter Gene Expression in the JAr Human Choriocarcinoma Cell Line Endocrinology, June 1, 2002; 143(6): 2216 - 2220. [Abstract] [Full Text] [PDF]

				V. Fatourechi, I. D. Hay, H. Javedan, G. A. Wiseman, B. P. Mullan, and C. A. Gorman Lack of Impact of Radioiodine Therapy in Tg-Positive, Diagnostic Whole-Body Scan-Negative Patients with Follicular Cell-Derived Thyroid Cancer J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1521 - 1526. [Abstract] [Full Text] [PDF]

				J. W. A. Smit, J. P. Schroder-van der Elst, M. Karperien, I. Que, M. Stokkel, D. van der Heide, and J. A. Romijn Iodide Kinetics and Experimental 131I Therapy in a Xenotransplanted Human Sodium-Iodide Symporter-Transfected Human Follicular Thyroid Carcinoma Cell Line J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1247 - 1253. [Abstract] [Full Text] [PDF]

				A. V. D'Elia, G. Tell, D. Russo, F. Arturi, F. Puglisi, G. Manfioletti, V. Gattei, D. L. Mack, P. Cataldi, S. Filetti, et al. Expression and Localization of the Homeodomain-Containing Protein HEX in Human Thyroid Tumors J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1376 - 1383. [Abstract] [Full Text] [PDF]

				M. Tonacchera, P. Viacava, P. Agretti, G. de Marco, A. Perri, C. di Cosmo, M. de Servi, P. Miccoli, F. Lippi, A. G. Naccarato, et al. Benign Nonfunctioning Thyroid Adenomas Are Characterized by a Defective Targeting to Cell Membrane or a Reduced Expression of the Sodium Iodide Symporter Protein J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 352 - 357. [Abstract] [Full Text] [PDF]

				M. R. Castro, E. R. Bergert, J. R. Goellner, I. D. Hay, and J. C. Morris Immunohistochemical Analysis of Sodium Iodide Symporter Expression in Metastatic Differentiated Thyroid Cancer: Correlation with Radioiodine Uptake J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5627 - 5632. [Abstract] [Full Text] [PDF]

				U. Haberkorn and A. Altmann Imaging Techniques for Gene Therapy: SPECT, PET, and MRI Journal of Pharmacy Practice, October 1, 2001; 14(5): 383 - 396. [Abstract] [PDF]

				T. Kogai, J. M. Hershman, K. Motomura, T. Endo, T. Onaya, and G. A. Brent Differential Regulation of the Human Sodium/Iodide Symporter Gene Promoter in Papillary Thyroid Carcinoma Cell Lines and Normal Thyroid Cells Endocrinology, August 1, 2001; 142(8): 3369 - 3379. [Abstract] [Full Text] [PDF]

				C. Spitzweg, K. J. Harrington, L. A. Pinke, R. G. Vile, and J. C. Morris The Sodium Iodide Symporter and Its Potential Role in Cancer Therapy J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3327 - 3335. [Full Text] [PDF]

				H. Shimura, H. Suzuki, A. Miyazaki, F. Furuya, K. Ohta, K. Haraguchi, T. Endo, and T. Onaya Transcriptional Activation of the Thyroglobulin Promoter Directing Suicide Gene Expression by Thyroid Transcription Factor-1 in Thyroid Cancer Cells Cancer Res., May 1, 2001; 61(9): 3640 - 3646. [Abstract] [Full Text]

				U. Haberkorn, M. Henze, A. Altmann, S. Jiang, I. Morr, M. Mahmut, P. Peschke, W. Kübler, J. Debus, and M. Eisenhut Transfer of the Human NaI Symporter Gene Enhances Iodide Uptake in Hepatoma Cells J. Nucl. Med., February 1, 2001; 42(2): 317 - 325. [Abstract] [Full Text]

				F. Grunwald and H.-J. Biersack FDG PET in Thyroid Cancer: Thyroxine or Not? J. Nucl. Med., December 1, 2000; 41(12): 1996 - 1998. [Full Text] [PDF]

				R. P. M. Biscolla, J. M. Cerutti, and R. M. B. Maciel Detection of Recurrent Thyroid Cancer by Sensitive Nested Reverse Transcription-Polymerase Chain Reaction of Thyroglobulin and Sodium/Iodide Symporter Messenger Ribonucleic Acid Transcripts in Peripheral Blood J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3623 - 3627. [Abstract] [Full Text]

				A. Boland, M. Ricard, P. Opolon, J.-M. Bidart, P. Yeh, S. Filetti, M. Schlumberger, and M. Perricaudet Adenovirus-mediated Transfer of the Thyroid Sodium/Iodide Symporter Gene into Tumors for a Targeted Radiotherapy Cancer Res., July 1, 2000; 60(13): 3484 - 3492. [Abstract] [Full Text]

				A. De la Vieja, O. Dohan, O. Levy, and N. Carrasco Molecular Analysis of the Sodium/Iodide Symporter: Impact on Thyroid and Extrathyroid Pathophysiology Physiol Rev, July 1, 2000; 80(3): 1083 - 1105. [Abstract] [Full Text] [PDF]

				J.-M. Bidart, C. Mian, V. Lazar, D. Russo, S. Filetti, B. Caillou, and M. Schlumberger Expression of Pendrin and the Pendred Syndrome (PDS) Gene in Human Thyroid Tissues J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 2028 - 2033. [Abstract] [Full Text]

				V. Lazar, J.-M. Bidart, B. Caillou, C. Mahé, L. Lacroix, S. Filetti, and M. Schlumberger Expression of the Na+/I- Symporter Gene in Human Thyroid Tumors: A Comparison Study with Other Thyroid-Specific Genes J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3228 - 3234. [Abstract] [Full Text]