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The study evaluates DN200434 in radioiodine-resistant papillary thyroid cancer cells by assessing ERRγ-mediated regulation of NIS function. Experiments measure iodide uptake, ERRγ/NIS and MAP pathway signaling, test MEK inhibition with U0126, and determine cytotoxicity using 131I clonogenic assays. DN200434 increases dose-dependent iodide uptake, ERK1/2 activation, membrane NIS localization, and 131I cytotoxicity.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/dn200434-an-inverse-agonist-of-estrogen-related-receptor-gamma-enhances-nai-symporter-function-through-mitogen-activated-protein-kinase-signaling-in-radioiodine-refractory-papillary-thyroid-cancer-cells/371121/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/dn200434-an-inverse-agonist-of-estrogen-related-receptor-gamma-enhances-nai-symporter-function-through-mitogen-activated-protein-kinase-signaling-in-radioiodine-refractory-papillary-thyroid-cancer-cells/371121.png","ImageObject",300,407,{"name":92,"@type":93},"pixelkiddo","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main objective of this study?","Question",{"text":112,"@type":113},"To determine how DN200434 affects ERRγ-mediated regulation of NIS function in radioiodine-refractory papillary thyroid cancer cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was NIS function measured after DN200434 treatment?",{"text":117,"@type":113},"By serially assessing radioiodine uptake in RAI-resistant BCPAP cells using a radioiodine uptake assay.",{"name":119,"@type":110,"acceptedAnswer":120},"What effect does MEK inhibition (U0126) have on DN200434 outcomes?",{"text":121,"@type":113},"U0126 overturns the increased radioiodine uptake and ERK1/2 activation induced by DN200434.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},371121,1790337046,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},962090883892,"https://ap-avatar.wpscdn.com/avatar/e00115db34f3e0f11b?x-image-process=image/resize,m_fixed,w_180,h_180&k=1790152879550218658","RESEARCH ARTICLE  \n\n| Editorial Proc | ess: Submission:02/11/2025 Acceptance:10/31/2025 Published:11/21/2025 |\n| --- | --- |\n\nDN200434: An Inverse Agonist of Estrogen Related Receptor Gamma Enhances Na+/I- symporter Function through Mitogen-Activated Protein Kinase Signaling in Radioiodine-Refractory Papillary Thyroid Cancer Cells  \nVijaya Sarangthem1,2, Priyanka Upadhyay3, Ridhima Goel3, Deepak Gulwani3, Thoudam Debraj Singh3 *  \nAbstract  \nBackground: Earlier, we have reported a series of inverse agonist of estrogen related receptor gamma (ERRγ), viz DN200434, GSK5182 and its derivates, that enhance sodium iodide (Na+/I-) symporter (NIS) function through mitogenactivated protein (MAP) kinase signaling in anaplastic thyroid cancer cells. But, the effect of our recently discovered DN200434, on NIS function in papillary thyroid cancer (PTC) refractory to radioactive iodine (RAI) therapy has not been reported. Herein, we studied the effects of DN200434 in RAI-resistant PTC cells on ERRγ-mediated regulation of NIS function. Methods: RAI-refractory BCPAP cells were exposed to lower concentrations of DN200434 and the NIS function in the PTC cells was serially assessed by radioiodine uptake assay. Immunoblot assay was performed to study the effect of DN200434 on ERRγ, NIS, the mitogen-activated protein (MAP) kinase pathway, and iodidehandling genes. To examine whether the DN200434-induced NIS functional activity can be affected by inhibition of the MAP kinase pathway, radioiodine uptake was performed after the application of U0126, a selective MEK inhibitor to DN200434-treated cells. Finally, the cytotoxic effect of 131I was determined in DN200434 treated and untreated cells by clonogenic assay. Results: Treatment of DN200434 resulted in dose-dependent increases in iodide uptake in BCPAP cells, downregulation ofERRγ protein and the activation of extracellular signal-regulated kinase (ERK) 1/2 . Treatment of the specific MEK inhibitor overturned the increased radioiodine uptake and ERK1/2 activation of BCPAP cells. DN200434 treatment enhanced the membrane localization of NIS in BCPAP cells. Clonogenic assay results revealed enhanced cytotoxic effects of 131I in DN200434 pre-exposed BCPAP cells. Conclusion: Thus, we successfully demonstrate that our novel inverse agonist ofERRγ, DN200434, enhances the responsiveness of radioiodine therapy by modulating NIS function in RAI-refractory papillary thyroid cancer cells via the regulation ofERRγ and the MAP kinase signaling pathway.  \nKeywords: Estrogen-related receptor gamma-sodium iodide symporter-radioiodine-radioiodine uptake  \nAsian Pac J Cancer Prev, 26 (11), 3987-3995  \nIntroduction  \nThyroid cancer is considered as the most common endocrine disorder in the last decade [1] . Thyroid cancers are classified based on their origin, and more than 80% of thyroid cancers are well-differentiated cancer that are derived from follicular epithelial cells such as papillary thyroid carcinoma (PTC), and follicular thyroid carcinoma (FTC). Anaplastic thyroid cancer (ATC) is undifferentiated cancer that consist of less than 5% and is highly lethal. Lack of deep molecular insight studies and existing primitive diagnostic tools contribute to the failure of the  \nclinical cure for radioiodine-refractory PTC and ATC [2] . Therefore, a better understanding of the signaling pathways during thyroid cancer development is required to identify new biomarker and therapeutic target for a novel therapeutic approach.  \nThe sodium iodide (Na+/I-) symporter (NIS) is atransmembrane glycoprotein which are endogenously expressed in normal thyroid and cancerous cells. NIS actively transport iodide into follicular cells of the thyroid gland as a normal process for thyroid hormone synthesis [3]. Over the years, endogenous NIS expression has been exploited for diagnosis purpose as well as radioiodine  \n1Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India. 2Department of Biochemistry a","cbCaifweG2rtwvkq","https://ap.wps.com/l/cbCaifweG2rtwvkq","pdf",1022495,"English","# Abstract\n# Introduction","[{\"question\":\"What is the main objective of this study?\",\"answer\":\"To determine how DN200434 affects ERRγ-mediated regulation of NIS function in radioiodine-refractory papillary thyroid cancer cells.\"},{\"question\":\"How was NIS function measured after DN200434 treatment?\",\"answer\":\"By serially assessing radioiodine uptake in RAI-resistant BCPAP cells using a radioiodine uptake assay.\"},{\"question\":\"What effect does MEK inhibition (U0126) have on DN200434 outcomes?\",\"answer\":\"U0126 overturns the increased radioiodine uptake and ERK1/2 activation induced by DN200434.\"}]","DN200434: An Inverse Agonist of Estrogen Related Receptor Gamma Enhances Na+/I- symporter Function through Mitogen-Activated Protein Kinase Signaling in Radioiodine-Refractory Papillary Thyroid Cancer Cells | PDF",1790191295,23]