Evidence for Transcriptional and Posttranscriptional Alterations of the Sodium/Iodide Symporter Expression in Hypofunctioning Benign and Malignant Thyroid Tumors

Trouttet-Masson, Séverine; Selmi-Ruby, Samia; Bernier-Valentin, Françoise; Porra, Valérie; N, Berger-Dutrieux; Decaussin, Myriam; Peix, Jean‐Louis; Perrin, Agnès; Bournaud, Claire; Orgiazzi, Jacques; Borson‐Chazot, Françoise; Franc, Brigitte; Rousset, Bernard

doi:10.1016/s0002-9440(10)63272-5

Cited by 52 publications

(40 citation statements)

References 40 publications

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“…Partially glycosylated NIS (50 kDa band) was detected in most of the carcinomas. Similar observations were reported by Trouttet-Masson and collaborators (14). They concluded that the impairment of NIS in thyroid tumours might result from alterations occurring at the transcriptional and post-transcriptional levels.…”

Section: Discussionsupporting

confidence: 87%

“…Most thyroid cancers are associated with a decreased iodide accumulation capacity appearing as 'cold' nodules. Following the identification of the human NIS cDNA, as reported by several groups (6)(7)(8)(9)(10)(11)(12)(13)(14), it is now well established that thyroid cancer cells have lower NIS mRNA levels than normal tissues, explaining the decreased iodide uptake. Several early publications reported a lower level of NIS protein expression in thyroid tumours (15)(16)(17), confirming the expected correlation between low levels of NIS mRNA, NIS protein and iodide accumulation.…”

Section: Introductionmentioning

confidence: 95%

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Immunoanalysis indicates that the sodium iodide symporter is not overexpressed in intracellular compartments in thyroid and breast cancers

Peyrottes

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Ondo-Méndez

et al. 2009

European Journal of Endocrinology

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Objective: The active transport of iodide into thyroid cells is mediated by the Na C /I K symporter (NIS) located in the basolateral membrane. Strong intracellular staining with anti-NIS antibodies has been reported in thyroid and breast cancers. Our initial objective was to screen tumour samples for intracellular NIS staining and then to study the mechanisms underlying the altered subcellular localization of the transporters. Methods: Immunostaining using three different anti-NIS antibodies was performed on paraffinembedded tissue sections from 93 thyroid or breast cancers. Western blot experiments were carried out to determine the amount of NIS protein in 20 samples. Results: Using three different anti-NIS antibodies, we observed intracellular staining in a majority of thyroid tumour samples. Control immunohistochemistry and western blot experiments indicated that this intracellular staining was due to non-specific binding of the antibodies. In breast tumours, very weak intracellular staining was observed in some samples. Western blot experiments suggest that this labelling is also non-specific. Conclusions: Our results strongly indicate that the NIS protein level is low in thyroid and breast cancers and that the intracellular staining obtained with anti-NIS antibodies corresponds to a non-specific signal. Accordingly, to increase the efficiency of radiotherapy for thyroid cancers and to enable the use of radioiodine in the diagnosis and therapy of breast tumours, improving NIS targeting to the plasma membrane will not be sufficient. Instead, increasing the expression level of NIS should remain the major goal of this field.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 95%

Immunoanalysis indicates that the sodium iodide symporter is not overexpressed in intracellular compartments in thyroid and breast cancers

Peyrottes

Navarro

Ondo-Méndez

et al. 2009

European Journal of Endocrinology

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“…This can be correlated with data in the human PTC. It could be due to an increased intracellular NIS misexpression (Saito et al, 1998;Wapnir et al, 2003;Riesco-Eizaguirre and Santisteban, 2006), to conformational changes (Gérard et al, 2003) or to the non maturation of hNIS (Trouttet-Masson et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Human thyroid tumours, the puzzling lessons from E7 and RET/PTC3 transgenic mice

et al. 2008

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Human rearranged RET/PTC3 (papillary thyroid carcinoma) proto-oncogene and high-risk human papillomavirus (HPV) type 16 E7 oncogene induces in the mouse a neoplastic transformation of thyroid follicular cells. We present a detailed immuno-histological study (170 mouse thyroids: RET/PTC3, E7, wild type, 2-to 10-month-old) with cell cycle proliferation and signalling pathway indicators. The characteristics of both models are different. There is an 'oncogene dependent' cellular signature, maintained at all studied ages in the E7 model, less in the RET/PTC3 model. During tumour development a large heterogeneity occurred in the Tg-RET/PTC3 model within a same tumour or within a same thyroid lobe. The Tg-E7 model was less heterogeneous, with a dominant goitrous pattern. The solid tumour already described in the RET/PTC3 models associated with cribriform patterns, suggested 'PTC spindle cell changes' as in humans PTC rather than the equivalent of the solid human PTC. Proliferation and apoptosis in the two thyroid models are related to the causal oncogene rather than reflect a general tumorigenic process. The thyroids of RET/PTC3 mice appeared as a partial and transient model of human PTCs, whereas the Tg-E7 mice do not belong to the usual PTC type.

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“…Harii et al also described a discrepancy between adenosine-induced iodide uptake activity and NIS protein levels (27). Furthermore, in thyroid tumors, weak intracellular radioiodine labeling has been shown to correspond to immature NIS protein that results from transcriptional and post-transcriptional alterations (43). Other reports suggested that the NIS protein is highly regulated by post-transcriptional events that control, in particular, its subcellular localization (36,44,45).…”

Section: Discussionmentioning

confidence: 99%

Propylthiouracil Increases Sodium/Iodide Symporter Gene Expression and Iodide Uptake in Rat Thyroid Cells in the Absence of TSH

Sue

Akama

Kawashima

et al. 2012

Thyroid

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Background: Propylthiouracil (PTU) and methimazole (MMI) are drugs that are widely used to treat Graves' disease. Although both exert an antithyroid effect primarily by blocking thyroid peroxidase activity, their molecular structure and other actions are different. We hypothesized that PTU and MMI may have differential effects on thyroid-specific gene expression and function. Methods: The effects of PTU and MMI on thyroid-specific gene expression and function were examined in rat thyroid FRTL-5 cells using DNA microarray, reverse transcriptase (RT)-polymerase chain reaction (PCR), real-time PCR, Western blot, immunohistochemistry, and radioiodine uptake studies. Results: DNA microarray analysis showed a marked increase in sodium/iodide symporter (NIS) gene expression after PTU treatment, whereas MMI had no effect. RT-PCR and real-time PCR analysis revealed that PTUinduced NIS mRNA levels were comparable to those elicited by thyroid-stimulating hormone (TSH). PTU increased 5¢-1880-bp and 5¢-1052-bp activity of the rat NIS promoter. While PTU treatment also increased NIS protein levels, the size of the induced protein was smaller than that induced by TSH, and the protein localized predominantly in the cytoplasm rather than the plasma membrane. Accumulation of 125 I in FRTL-5 cells was increased by PTU stimulation, but this effect was weaker than that produced by TSH. Conclusions: We found that PTU induces NIS expression and iodide uptake in rat thyroid FRTL-5 cells in the absence of TSH. Although PTU and MMI share similar antithyroid activity, their effects on other thyroid functions appear to be quite different, which could affect their therapeutic effectiveness.

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Evidence for Transcriptional and Posttranscriptional Alterations of the Sodium/Iodide Symporter Expression in Hypofunctioning Benign and Malignant Thyroid Tumors

Cited by 52 publications

References 40 publications

Immunoanalysis indicates that the sodium iodide symporter is not overexpressed in intracellular compartments in thyroid and breast cancers

Immunoanalysis indicates that the sodium iodide symporter is not overexpressed in intracellular compartments in thyroid and breast cancers

Human thyroid tumours, the puzzling lessons from E7 and RET/PTC3 transgenic mice

Propylthiouracil Increases Sodium/Iodide Symporter Gene Expression and Iodide Uptake in Rat Thyroid Cells in the Absence of TSH

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