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Aparna Lakshmanan, Anna Wojcicka, Marta Kotlarek, Xiaoli Zhang, Krystian Jazdzewski, and Sissy M Jhiang

Introduction Na + /I − symporter (NIS)-mediated radioiodide uptake (RAIU) in thyroid cells allows for targeted treatment of thyroid cancer. Many patients with advanced thyroid cancer do not benefit from radioiodine therapy due to reduced

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Christina Schug, Sarah Urnauer, Carsten Jaeckel, Kathrin A Schmohl, Mariella Tutter, Katja Steiger, Nathalie Schwenk, Markus Schwaiger, Ernst Wagner, Peter J Nelson, and Christine Spitzweg

. The resulting clones were isolated and analyzed for NIS-mediated radioiodide uptake activity using an iodide uptake assay (see below). Among ~40 screened colonies, the stably transfected cell clone with the highest levels of iodide accumulation was

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W Imruetaicharoenchoke, A Fletcher, W Lu, R J Watkins, B Modasia, V L Poole, H R Nieto, R J Thompson, K Boelaert, M L Read, V E Smith, and C J McCabe

et al . 2007 ). PBF also binds to the sodium iodide symporter (NIS) and monocarboxylate transporter 8 (MCT8), modulating their subcellular localisation, and regulating radioiodide uptake and thyroid hormone efflux, respectively ( Smith et al . 2009

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Douangsone D Vadysirisack, Anjli Venkateswaran, Zhaoxia Zhang, and Sissy M Jhiang

metastatic thyroid cancers. However, NIS expression, as well as NIS-mediated radioiodide uptake (RAIU) activity, is lost in some patients with advanced thyroid cancers, such that these patients cannot benefit from radioiodine imaging and therapy ( Arturi

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T Kogai, K Taki, and G A Brent

al. 1997 , Saito et al. 1997 , Pekary & Hershman 1998 ). The influence of TSH on the stimulation of radioiodide uptake in metastatic thyroid cancer has been recognized, since radioiodine was first used in the 1950s. TSH stimulation is achieved by

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Yu-Yu Liu, Xiaoli Zhang, Matthew D Ringel, and Sissy M Jhiang

parental thyroid cells, albeit with different magnitude and temporal dynamics ( Garcia & Santisteban 2002 , Knauf et al . 2003 , Vadysirisack et al . 2007 b ). NIS-mediated radioiodide uptake (RAIU) was transiently decreased at 4 h, but increased at 24

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Sissy M Jhiang and Jennifer A Sipos

precursor cells are committed to the differentiated gastric mucosa. NIS expression in breast tissues NIS expression and radioiodide uptake in breast tissues are at the highest levels during active lactation ( Cho et al. 2000 , Tazebay et al

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Garcilaso Riesco-Eizaguirre, Pilar Santisteban, and Antonio De la Vieja

). Inhibitors for PI3K, AKT, or mTORC1 increase iodide uptake in thyroid PCCL3 cells under chronic TSH stimulation. However, although AKT inhibition increases NIS-mediated radioiodide uptake, it does not increase NIS protein levels ( Liu et al. 2012 ). The

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Yu-Yu Liu, Michael P Brandt, Daniel H Shen, Richard T Kloos, Xiaoli Zhang, and Sissy M Jhiang

. unpublished observations 2010) as well as NIS-mediated radioiodide uptake activity ( Kogai et al . 2008 , Liu et al . unpublished observations 2010). Although thyroidal NIS expression was increased by mitogen-activated protein kinase (MAPK) inhibitors

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Wei Li and Kenneth B Ain

protein as measured by western blot. In addition, evaluation of radioiodide uptake in these cells after this treatment failed to reveal any significant uptake (data not shown). Discussion Radioiodine therapy remains the only known effective systemic