Retinoic Acid Increases Sodium/Iodide Symporter mRNA Levels in Human Thyroid Cancer Cell Lines and Suppresses Expression of Functional Symporter in Nontransformed FRTL-5 Rat Thyroid Cells

1998 ◽  
Vol 246 (2) ◽  
pp. 562
Author(s):  
C. Schmutzler ◽  
R. Winzer ◽  
J. Meissner-Weigl ◽  
J. Köhrle
Keyword(s):  
Thyroid Cancer ◽  
Retinoic Acid ◽  
Sodium Iodide ◽  
Human Thyroid ◽  
Mrna Levels ◽  
Thyroid Cancer Cell ◽  
Sodium Iodide Symporter ◽  
Thyroid Cells ◽  
Thyroid Cancer Cell Lines ◽  
Rat Thyroid

scholarly journals Histone deacetylation of NIS promoter underlies BRAF V600E-promoted NIS silencing in thyroid cancer

2013 ◽  
Vol 21 (2) ◽  
pp. 161-173 ◽  
Author(s):  
Zongjing Zhang ◽  
Dingxie Liu ◽  
Avaniyapuram Kannan Murugan ◽  
Zhimin Liu ◽  
Mingzhao Xing
Keyword(s):  
Thyroid Cancer ◽  
Histone Acetylation ◽  
Underlying Mechanism ◽  
Histone Deacetylation ◽  
Braf V600e ◽  
Epigenetic Mechanism ◽  
Human Thyroid ◽  
Sodium Iodide Symporter ◽  
Thyroid Cells ◽  
Rat Thyroid

The BRAF V600E mutation causes impaired expression of sodium iodide symporter (NIS) and radioiodine refractoriness of thyroid cancer, but the underlying mechanism remains undefined. In this study, we hypothesized that histone deacetylation at the NIS (SLC5A5) promoter was the mechanism. Using the chromatin immunoprecipitation approach, we examined histone acetylation status on the lysine residues H3K9/14, H3K18, total H4, and H4K16 at the NIS promoter under the influence of BRAF V600E. We found that expression of stably or transiently transfected BRAF V600E inhibited NIS expression while the deacetylase inhibitor SAHA stimulated NIS expression in PCCL3 rat thyroid cells. Although BRAF V600E enhanced global histone acetylation, it caused histone deacetylation at the NIS promoter while SAHA caused acetylation in the cells. In human thyroid cancer BCPAP cells harboring homozygous BRAF V600E mutation, BRAF V600E inhibitor, PLX4032, and MEK inhibitor, AZD6244, increased histone acetylation of the NIS promoter, suggesting that BRAF V600E normally maintained histone in a deacetylated state at the NIS promoter. The regions most commonly affected with deacetylation by BRAF V600E were the transcriptionally active areas upstream of the translation start that contained important transcription factor binding sites, including nucleotides −297/−107 in the rat NIS promoter and −692/−370 in the human NIS promoter. Our findings not only reveal an epigenetic mechanism for BRAF V600E-promoted NIS silencing involving histone deacetylation at critical regulatory regions of the NIS promoter but also provide further support for our previously proposed combination therapy targeting major signaling pathways and histone deacetylase to restore thyroid gene expression for radioiodine treatment of thyroid cancer.

scholarly journals Selumetinib Activity in Thyroid Cancer Cells: Modulation of Sodium Iodide Symporter and Associated miRNAs

2018 ◽  
Vol 19 (7) ◽  
pp. 2077 ◽  
Author(s):  
Sabine Wächter ◽  
Annette Wunderlich ◽  
Brandon Greene ◽  
Silvia Roth ◽  
Moritz Elxnat ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Sodium Iodide ◽  
Thyroid Cancer Cell ◽  
Sodium Iodide Symporter ◽  
Radioiodine Uptake ◽  
Thyroid Cancer Cell Lines ◽  
Thyroid Cancer Cells

Background: The MEK (mitogen-activated protein kinase)–inhibitor selumetinib led to increased radioiodine uptake and retention in a subgroup of patients suffering from radioiodine refractory differentiated thyroid cancer (RR-DTC). We aimed to analyse the effect of selumetinib on the expression of sodium iodide symporter (NIS; SLC5A5) and associated miRNAs in thyroid cancer cells. Methods: Cytotoxicity was assessed by viability assay in TPC1, BCPAP, C643 and 8505C thyroid cancer cell lines. NIS, hsa-let-7f-5p, hsa-miR-146b-5p, and hsa-miR-146b-3p expression was determined by quantitative RT-PCR. NIS protein was detected by Western blot. Radioiodine uptake was performed with a Gamma counter. Results: Selumetinib caused a significant reduction of cell viability in all thyroid cancer cell lines. NIS transcript was restored by selumetinib in all cell lines. Its protein level was found up-regulated in TPC1 and BCPAP cells and down-regulated in C643 and 8505C cells after treatment with selumetinib. Treatment with selumetinib caused a down-regulation of hsa-let-7f-5p, hsa-miR-146b-5p and hsa-miR-146b-3p in TPC1 and BCPAP cells. In 8505C cells, a stable or down-regulated hsa-miR-146b-5p was detected after 1h and 48h of treatment. C643 cells showed stable or up-regulated hsa-let-7f-5p, hsa-miR-146b-5p and hsa-miR-146b-3p. Selumetinib treatment caused an increase of radioiodine uptake, which was significant in TPC1 cells. Conclusions: The study shows for the first time that selumetinib restores NIS by the inhibition of its related targeting miRNAs. Further studies are needed to clarify the exact mechanism activated by hsa-miR-146b-5p, hsa-miR-146b-3p and hsa-let7f-5p to stabilise NIS. Restoration of NIS could represent a milestone for the treatment of advanced RR-DTC.

scholarly journals Different expression of TSH receptor and NIS genes in thyroid cancer: role of epigenetics

2013 ◽  
Vol 52 (2) ◽  
pp. 121-131 ◽  
Author(s):  
Maria D'Agostino ◽  
Marialuisa Sponziello ◽  
Cinzia Puppin ◽  
Marilena Celano ◽  
Valentina Maggisano ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Tsh Receptor ◽  
Human Thyroid ◽  
Mrna Levels ◽  
Thyroid Cancer Cell ◽  
Post Translational Modifications ◽  
Thyroid Cancer Cell Lines

The TSH receptor (TSHR) and sodium/iodide symporter (NIS) are key players in radioiodine-based treatment of differentiated thyroid cancers. While NIS (SLC5AS) expression is diminished/lost in most thyroid tumors, TSHR is usually preserved. To examine the mechanisms that regulate the expression of NIS and TSHR genes in thyroid tumor cells, we analyzed their expression after inhibition of ras–BRAF–MAPK and PI3K–Akt–mTOR pathways and the epigenetic control occurring at the gene promoter level in four human thyroid cancer cell lines. Quantitative real-time PCR was used to measure NIS and TSHR mRNA in thyroid cancer cell lines (TPC-1, BCPAP, WRO, and FTC-133). Western blotting was used to assess the levels of total and phosphorylated ERK and Akt. Chromatin immunoprecipitation was performed for investigating histone post-translational modifications of the TSHR and NIS genes. ERK and Akt inhibitors elicited different responses of the cells in terms of TSHR and NIS mRNA levels. Akt inhibition increased NIS transcript levels and reduced those of TSHR in FTC-133 cells but had no significant effects in BCPAP. ERK inhibition increased the expression of both genes in BCPAP cells but had no effects in FTC-133. Histone post-translational modifications observed in the basal state of the four cell lines as well as in BCPAP treated with ERK inhibitor and FTC-133 treated with Akt inhibitor show cell- and gene-specific differences. In conclusion, our data indicate that in thyroid cancer cells the expression of TSHR and NIS genes is differently controlled by multiple mechanisms, including epigenetic events elicited by major signaling pathways involved in thyroid tumorigenesis.

scholarly journals Comprehensive Genetic Characterization of Human Thyroid Cancer Cell Lines: A Validated Panel for Preclinical Studies

2019 ◽  
Vol 25 (10) ◽  
pp. 3141-3151 ◽  
Author(s):  
Iñigo Landa ◽  
Nikita Pozdeyev ◽  
Christopher Korch ◽  
Laura A. Marlow ◽  
Robert C. Smallridge ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Genetic Characterization ◽  
Cancer Cell Lines ◽  
Human Thyroid ◽  
Preclinical Studies ◽  
Thyroid Cancer Cell ◽  
Thyroid Cancer Cell Lines

scholarly journals 5-Aza-2′-Deoxycytidine Has Minor Effects on Differentiation in Human Thyroid Cancer Cell Lines, But Modulates Genes That Are Involved in Adaptation In Vitro

Thyroid ◽  
2013 ◽  
Vol 23 (3) ◽  
pp. 317-328 ◽  
Author(s):  
Geneviève Dom ◽  
Vanessa Chico Galdo ◽  
Maxime Tarabichi ◽  
Gil Tomás ◽  
Aline Hébrant ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Thyroid ◽  
Thyroid Cancer Cell ◽  
Thyroid Cancer Cell Lines

scholarly journals Genetics of Human Thyroid Cancer Cell Lines—Response

2019 ◽  
Vol 25 (22) ◽  
pp. 6883-6884
Author(s):  
Iñigo Landa ◽  
Nikita Pozdeyev ◽  
Jeffrey A. Knauf ◽  
Bryan R. Haugen ◽  
James A. Fagin ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Thyroid ◽  
Thyroid Cancer Cell ◽  
Thyroid Cancer Cell Lines

scholarly journals Induction of apoptosis and necrosis by zinc in human thyroid cancer cell lines

2001 ◽  
Vol 169 (2) ◽  
pp. 417-424 ◽  
Author(s):  
M Iitaka ◽  
S Kakinuma ◽  
S Fujimaki ◽  
I Oosuga ◽  
T Fujita ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Thyroid ◽  
Dependent Manner ◽  
Thyroid Cancer Cell ◽  
Thyroid Cancer Cell Lines ◽  
Thyroid Cancer Cells

Zinc at concentrations of 150, microM or higher induced necrosis as well as apoptosis in thyroid cancer cell lines. Necrosis was induced by zinc in a dose-dependent manner, whereas apoptosis did not increase at higher concentrations of zinc. The expression of the antiapoptotic protein phosphorylated Bad was markedly increased, whereas the expression of the proapoptotic proteins Bax and Bad decreased following Zn(2+) exposure. Zn(2+) induced rapid degradation of IkappaB, and an increase in the binding of nuclear transcription factor-kappaB (NF-kappaB). These observations indicate that antiapoptotic pathways were activated in thyroid cancer cells following exposure to Zn(2+). This may be a self-defence mechanism against apoptosis and may underlie the general resistance of thyroid cancer cells to apoptotic stimuli. Zinc may be a potential cytotoxic agent for the treatment of thyroid cancer.

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