Inverse Agonist of Estrogen-Related Receptor γ Enhances Sodium Iodide Symporter Function Through Mitogen-Activated Protein Kinase Signaling in Anaplastic Thyroid Cancer Cells

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
Thoudam Debraj SinghYoung Hyun Jeon

Abstract

Anaplastic thyroid cancer (ATC), a rare thyroid cancer with poor prognosis, is associated with insufficient function of the sodium iodide symporter (NIS). Estrogen-related receptor γ (ERRγ) is a member of the orphan nuclear receptors with important functions in cell development and homeostasis. However, there are no reports that demonstrate whether ERRγ is related to NIS function. Here, we evaluated the role of ERRγ in the regulation of NIS function in ATC cells using GSK5182, an inverse agonist of ERRγ. Two ATC cell lines, BHT-101 and CAL62, were incubated with GSK5182 at various time points and doses. The NIS function in the ATC cells was serially assessed by their uptake of radioiodine. The effects of GSK5182 on ERRγ and the mitogen-activated protein (MAP) kinase pathway, as well as on NIS protein, were evaluated by immunoblot assay. To examine whether the GSK5182-induced NIS functional activity can be affected by inhibition of the MAP kinase pathway, the MAP kinase activity and levels of radioiodine uptake were determined after application of a mitogen-activated protein kinase kinase (MEK) inhibitor to GSK5182-treated cells. Finally, the cytotoxic effect of (131)I was determined by clonogenic assay. Treatment with GSK5182 r...Continue Reading

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Citations

Jan 16, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jina KimSung Jin Cho
Jun 27, 2006·The Journal of Steroid Biochemistry and Molecular Biology·Jungyoon ChoYoung Joo Lee
Nov 1, 2017·Frontiers in Endocrinology·Chae Moon Hong, Byeong-Cheol Ahn
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Oct 27, 2018·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Francesco De RoseCalogero D'Alessandria
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Jul 3, 2021·Cancers·Yuchen JinWeijun Wei
May 21, 2020·Molecular Pharmaceutics·Louis Allott, Eric O Aboagye

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