Semi-quantitative comparison of the differentiation markers and sodium iodide symporter messenger ribonucleic acids in papillary thyroid carcinomas using RT-PCR

Tanaka, Katsuhiro; Otsuki, Takemi; Sonoo, Hiroshi; Yamamoto, Yutaka; Udagawa, Kiyoshi; Kunisue, Hironori; Arime, Ichiro; Yamamoto, Shigeru; Kurebayashi, Junichi; Shimozuma, Kojiro

doi:10.1530/eje.0.1420340

Cited by 34 publications

(21 citation statements)

References 33 publications

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“…The ability of the thyroid to accumulate iodide has provided an effective means for therapeutic doses of radioiodine to target and destroy iodide-transporting differentiated thyroid cancers and their metastases. However, most thyroid tumours exhibit reduced iodide uptake, although mRNA (Smanik et al, 1997;Lazar et al, 1999;Ryu et al, 1999;Arturi et al, 2000;Park et al, 2000;Tanaka et al, 2000) and protein (Caillou et al, 1998;Jhiang et al, 1998;Saito et al, 1998;Castro et al, 1999) studies have demonstrated inconsistent findings regarding reduction of NIS expression in thyroid cancer per se.…”

Section: Discussionmentioning

confidence: 99%

PTTG and PBF repress the human sodium iodide symporter

et al. 2007

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The ability of the thyroid to accumulate iodide provides the basis for radioiodine ablation of differentiated thyroid cancers and their metastases. Most thyroid tumours exhibit reduced iodide uptake, although the mechanisms accounting for this remain poorly understood. Pituitary tumour transforming gene (PTTG) is a proto-oncogene implicated in the pathogenesis of thyroid tumours. We now show that PTTG and its binding factor PBF repress expression of sodium iodide symporter (NIS) messenger RNA (mRNA), and inhibit iodide uptake. This process is mediated at least in part through fibroblast growth factor-2. In detailed studies of the NIS promoter in rat FRTL-5 cells, PTTG and PBF demonstrated specific inhibition of promoter activity via the human upstream enhancer element (hNUE). Within this B1 kb element, a complex PAX8-upstream stimulating factor 1 (USF1) response element proved critical both to basal promoter activity and to PTTG and PBF repression of NIS. In particular, repression by PTTG was contingent upon the USF1, but not the PAX8, site. Finally, in human primary thyroid cells, PTTG and PBF similarly repressed the NIS promoter via hNUE. Taken together, our data suggest that the reported overexpression of PTTG and PBF in differentiated thyroid cancer has profound implications for activity of the NIS gene, and hence significantly impacts upon the efficacy of radioiodine treatment.

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Section: Discussionmentioning

confidence: 99%

PTTG and PBF repress the human sodium iodide symporter

et al. 2007

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“…The expression of NIS in thyroid tumours has been investigated by different groups, with variable results. In particular, in a subset of either adenomas or carcinomas, NIS expression appeared to be reduced compared with the corresponding normal tissue (2 -6) or nil (7,8) whereas, in other cases, NIS was equally expressed or overexpressed compared with the normal tissue (9,10). In the latter case, NIS protein showed a defective targeting to the cell membrane and was mostly located inside the cytoplasm.…”

Section: Introductionmentioning

confidence: 92%

Expression of cAMP response element-binding protein and sodium iodide symporter in benign non-functioning and malignant thyroid tumours

Luciani

Buci²,

Conforti³

et al. 2003

European Journal of Endocrinology

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Objective: Reduced expression or defective targeting of the sodium/iodide symporter (NIS) to the cell membrane in thyroid tumours has been reported. 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. The cAMPdependent transcription factor cAMP response element-binding protein (CREB) binds to CRE acting, upon phosphorylation, as a transcriptional activator. In this study we evaluated the expression of CREB and NIS gene in thyroid non-functioning adenomas ðn ¼ 18Þ and carcinomas ðn ¼ 20Þ; as well as in the corresponding normal tissue. Methods: The levels of CREB and NIS mRNA were determined by quantitative real-time RT-PCR, whereas CREB protein (total and phosphorylated) was analyzed by Western blot. Results: The levels of CREB mRNA in thyroid carcinomas, but not in adenomas, were significantly lower than in the corresponding normal tissue ð4:63^0:89 vs 9:51^2:01 pg/mg total RNA, meansŜ .E., P ¼ 0:025Þ: CREB protein levels, which were determined in a subset of samples, were in quite good agreement with mRNA data. NIS mRNA levels did not differ in adenomas or carcinomas, compared with the corresponding normal tissue and no significant relationship with the levels of CREB mRNA was observed. 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.

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“…There is now abundant literature on human NIS (hNIS) expression in normal and pathological thyroid tissues. A series of articles analyzing hNIS transcript levels by reverse transcriptase-polymerase chain reaction (RT-PCR) [3][4][5][6][7][8] or tissue distribution of hNIS immunoreactivity on paraffin-embedded tissue sections 9 -12 report a general decrease in, sometimes a loss of hNIS expression in benign and malignant thyroid tumors. These data are in keeping with the fact that both benign [follicular adenomas (FAs)] and malignant (papillary and follicular carcinomas) thyroid tumors, with very few exceptions, exhibit a decrease up to a loss of iodide uptake activity.…”

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confidence: 99%