scholarly journals NADPH Oxidase NOX4 Is a Critical Mediator of BRAFV600E-Induced Downregulation of the Sodium/Iodide Symporter in Papillary Thyroid Carcinomas

2017 ◽  
Vol 26 (15) ◽  
pp. 864-877 ◽  
Author(s):  
Naïma Azouzi ◽  
Jérémy Cailloux ◽  
Juliana M. Cazarin ◽  
Jeffrey A. Knauf ◽  
Jennifer Cracchiolo ◽  
...  
1998 ◽  
Vol 101 (7) ◽  
pp. 1296-1300 ◽  
Author(s):  
T Saito ◽  
T Endo ◽  
A Kawaguchi ◽  
M Ikeda ◽  
R Katoh ◽  
...  

Thyroid ◽  
2000 ◽  
Vol 10 (3) ◽  
pp. 211-217 ◽  
Author(s):  
Hyun-Joo Park ◽  
Jin Yup Kim ◽  
Ki Young Park ◽  
Gyungyub Gong ◽  
Suk Joon Hong ◽  
...  

2020 ◽  
Vol 295 (31) ◽  
pp. 10726-10740
Author(s):  
Hongwei Gao ◽  
Peirong Bai ◽  
Lin Xiao ◽  
Mengjia Shen ◽  
Qiuxiao Yu ◽  
...  

Mediator complex subunit 16 (MED16) is a component of the mediator complex and functions as a coactivator in transcriptional events at almost all RNA polymerase II–dependent genes. In this study, we report that the expression of MED16 is markedly decreased in papillary thyroid cancer (PTC) tumors compared with normal thyroid tissues. In vitro, MED16 overexpression in PTC cells significantly inhibited cell migration, enhanced sodium/iodide symporter expression and iodine uptake, and decreased resistance to radioactive 131I (RAI). Conversely, PTC cells in which MED16 had been further knocked down (MED16KD) exhibited enhanced cell migration, epithelial–mesenchymal transition, and RAI resistance, accompanied by decreased sodium/iodide symporter levels. Moreover, cell signaling through transforming growth factor β (TGF-β) was highly activated after the MED16 knockdown. Similar results were obtained in MED12KD PTC cells, and a co-immunoprecipitation experiment verified interactions between MED16 and MED12 and between MED16 and TGF-βR2. Of note, the application of LY2157299, a potent inhibitor of TGF-β signaling, significantly attenuated MED16KD-induced RAI resistance both in vitro and in vivo. In conclusion, our findings indicate that MED16 reduction in PTC contributes to tumor progression and RAI resistance via the activation of the TGF-β pathway.


Surgery ◽  
2020 ◽  
Vol 167 (1) ◽  
pp. 56-63 ◽  
Author(s):  
Timothy M. Ullmann ◽  
Heng Liang ◽  
Maureen D. Moore ◽  
Isra Al-Jamed ◽  
Katherine D. Gray ◽  
...  

2010 ◽  
Vol 17 (2) ◽  
pp. 383-398 ◽  
Author(s):  
Wei Li ◽  
Kenneth B Ain

Radioiodine remains the only tumoricidal therapy for disseminated thyroid carcinomas; however, dedifferentiated tumors lose the expression of human sodium–iodide symporter (hNIS) gene, and cannot respond to this treatment. Previous studies suggested that a trans-active protein factor (NIS-repressor) represses endogenous hNIS transcription, likely contributing to the loss of radioiodine uptake, and defined the NIS-repressor binding site (NRBS) in the proximal hNIS promoter. Using electrophoretic mobility shift assay (EMSA), we found evidence of NIS-repressor in the nuclear extract from KAK-1 cells, and confirmed this result using nuclear extracts prepared from multiple verified thyroid cell lines. Luciferase reporter assays of hNIS promoter constructs and EMSA were used to define two core sequences, NRBS-P and NRBS-D, in the hNIS promoter as the binding sites for NIS-repressor. Electrophoretic analysis of KAK-1 nuclear extract proteins cross-linked with NRBS-P suggests that NIS-repressor is a protein complex. Analysis of KAK-1 nuclear extract proteins bound to NRBS-P, via liquid chromatography coupled with tandem mass spectroscopy, demonstrated poly(ADP-ribose) polymerase-1 (PARP-1) as a NIS-repressor component. Pharmacological inhibition of PARP-1 enzymatic activity using PJ34 stimulated both the luciferase reporter activity driven by hNIS promoter and the endogenous hNIS mRNA level. Supershift studies suggest that thyroid transcription factor 2 (TTF-2) is also associated with the NIS-repressor complex. NIS-repressor, including its PARP-1 component, presents a potential therapeutic target to restore radioiodine uptake in dedifferentiated thyroid carcinomas.


Thyroid ◽  
2010 ◽  
Vol 20 (9) ◽  
pp. 965-974 ◽  
Author(s):  
Mike S. Fenton ◽  
Kenneth M. Marion ◽  
Andrew K. Salem ◽  
Rachel Hogen ◽  
Faramarz Naeim ◽  
...  

Thyroid ◽  
2001 ◽  
Vol 11 (1) ◽  
pp. 37-39 ◽  
Author(s):  
Diego Russo ◽  
Diana Manole ◽  
Franco Arturi ◽  
Horacio G. Suarez ◽  
Martin Schlumberger ◽  
...  

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