Related Experiment Video
Updated: Jan 10, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
DN200434: An Inverse Agonist of Estrogen Related Receptor Gamma Enhances Na+/I- symporter Function through
Vijaya Sarangthem1,2, Priyanka Upadhyay3, Ridhima Goel3
1Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
Background:
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 mitogen-activated 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 iodide-handling 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 of ERRγ 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 of ERRγ, DN200434, enhances the responsiveness of radioiodine therapy by modulating NIS function in RAI-refractory papillary thyroid cancer cells via the regulation of ERRγ and the MAP kinase signaling pathway.
More Related Videos
10:04Radionuclide-fluorescence Reporter Gene Imaging to Track Tumor Progression in Rodent Tumor Models
Published on: March 13, 2018
08:48An In Vitro Dormancy Model of Estrogen-sensitive Breast Cancer in the Bone Marrow: A Tool for Molecular Mechanism Studies and Hypothesis Generation
Published on: June 30, 2015
Related Concept Videos
02:38Mitogens and the Cell Cycle
01:31Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
01:27Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
01:20Synthesis and Regulation of Thyroid Hormones
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
01:26Signal Transduction: Overview
Typically, signal transduction involves three...