Id1 Gene Expression Is Up-Regulated in Hyperplastic and Neoplastic Thyroid Tissue and Regulates Growth and Differentiation in Thyroid Cancer Cells

Thyroid cancer is the most abundant tumor of the endocrine organs. Poorly differentiated thyroid cancer is still difficult to treat. Human cells exposed to long-term real (r-) and simulated (s-) microgravity (µg) revealed morphological alterations and changes in the expression profile of genes involved in several biological processes. The objective of this study was to examine the effects of short-term µg on poorly differentiated follicular thyroid cancer cells (FTC-133 cell line) resulting from 6 min of exposure to µg on a sounding rocket flight. As sounding rocket flights consist of several flight phases with different acceleration forces, rigorous control experiments are mandatory. Hypergravity (hyper-g) experiments were performed at 18g on a centrifuge in simulation of the rocket launch and s-µg was simulated by a random positioning machine (RPM). qPCR analyses of selected genes revealed no remarkable expression changes in controls as well as in hyper-g samples taken at the end of the first minute of launch. Using a centrifuge initiating 18g for 1 min, however, presented moderate gene expression changes, which were significant for COL1A1, VCL, CFL1, PTK2, IL6, CXCL8 and MMP14. We also identified a network of mutual interactions of the investigated genes and proteins by employing in-silico analyses. Lastly, µg-samples indicated that microgravity is a stronger regulator of gene expression than hyper-g.

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Downregulated LRRK2 gene expression inhibits proliferation and migration while promoting the apoptosis of thyroid cancer cells by inhibiting activation of the JNK signaling pathway

International Journal of Oncology ◽

10.3892/ijo.2019.4816 ◽

2019 ◽

Cited By ~ 1

Author(s):

Zheng‑Cai Jiang ◽

Xiao‑Jun Chen ◽

Qi Zhou ◽

Xiao‑Hua Gong ◽

Xiong Chen ◽

...

Keyword(s):

Gene Expression ◽

Thyroid Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Jnk Signaling ◽

Lrrk2 Gene ◽

Jnk Signaling Pathway ◽

And Migration ◽

Thyroid Cancer Cells ◽

Proliferation And Migration

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Induction of Thyroid Gene Expression and Radioiodine Uptake in Thyroid Cancer Cells by Targeting Major Signaling Pathways

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2009-1888 ◽

2010 ◽

Vol 95 (2) ◽

pp. 820-828 ◽

Cited By ~ 62

Author(s):

Peng Hou ◽

Ermal Bojdani ◽

Mingzhao Xing

Keyword(s):

Gene Expression ◽

Thyroid Cancer ◽

Cancer Cells ◽

Signaling Pathways ◽

Histone Deacetylase ◽

Sodium Iodide ◽

Therapeutic Potential ◽

Sodium Iodide Symporter ◽

Thyroid Cells ◽

Thyroid Cancer Cells

Abstract Context: Radioiodine ablation is commonly used to treat thyroid cancer, but a major challenge is often the loss of radioiodine avidity of the cancer caused by aberrant silencing of iodide-handling genes. Objectives: This study was conducted to test the therapeutic potential of targeting the aberrantly activated MAPK and PI3K/Akt/mTOR pathways and histone deacetylase to restore radioiodine avidity in thyroid cancer cells. Experimental Design: We tested the effects of specific inhibitors targeting these pathways/molecules that had established clinical applicability, including the MAPK kinase inhibitor RDEA119, mTOR inhibitor temsirolimus, Akt inhibitor perifosine, and histone deacetylase inhibitor SAHA, individually or in combinations, on the expression of iodide-handling genes and radioiodide uptake in a large panel of thyroid cancer cell lines. Results: The expression of a large number of iodide-handling genes could be restored, particularly the sodium/iodide symporter, TSH receptor, and thyroperoxidase, by treating cells with these inhibitors. The effect was particularly robust and synergistic when combinations of inhibitors containing SAHA were used. Robust expression of sodium/iodide symporter in the cell membrane, which plays the most important role in iodide uptake in thyroid cells, was confirmed by immunofluorescent microscopy. Radioiodide uptake by cells was correspondingly induced under these conditions. Thyroid gene expression and radioiodide uptake could both be further enhanced by TSH. Conclusions: Targeting major signaling pathways could restore thyroid gene expression and radioiodide uptake in thyroid cancer cells. Further studies are warranted to test this therapeutic potential in restoring radioiodine avidity of thyroid cancer cells for effective ablation treatment.

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The peroxisome proliferator-activated receptor gamma agonist rosiglitazone inhibits growth and downregulates Bcl-2 gene expression in human follicular thyroid cancer cells

Annals of Surgical Oncology ◽

10.1007/bf02524134 ◽

2004 ◽

Vol 11 (S2) ◽

pp. S103-S103

Author(s):

W. T. Shen ◽

T. S. Wong ◽

M. G. Wong ◽

E. Kebebew ◽

Q. Y. Duh ◽

...

Keyword(s):

Gene Expression ◽

Thyroid Cancer ◽

Cancer Cells ◽

Peroxisome Proliferator ◽

Follicular Thyroid Cancer ◽

Peroxisome Proliferator Activated Receptor ◽

Thyroid Cancer Cells

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Inhibition of gap junction transfer sensitizes thyroid cancer cells to anoikis

Endocrine Related Cancer ◽

10.1530/erc-10-0289 ◽

2011 ◽

Vol 18 (5) ◽

pp. 613-626 ◽

Cited By ~ 16

Author(s):

Kirk Jensen ◽

Aneeta Patel ◽

Joanna Klubo-Gwiezdzinska ◽

Andrew Bauer ◽

Vasyl Vasko

Keyword(s):

Thyroid Cancer ◽

Gap Junction ◽

Cancer Cells ◽

Cancer Cell ◽

Thyroid Tissue ◽

Human Thyroid ◽

Thyroid Cancer Cell ◽

Gap Junctional ◽

Thyroid Cancer Cells

Resistance to anoikis (matrix deprivation-induced apoptosis) is a critical component of the metastatic cascade. Molecular mechanisms underlying resistance to anoikis have not been reported in thyroid cancer cells. For an in vitro model of anoikis, we cultured follicular, papillary, and anaplastic thyroid cancer cell lines on poly-HEMA-treated low-adherent plates. We also performed immunohistochemical analysis of human cancer cells that had infiltrated blood and/or lymphatic vessels. Matrix deprivation was associated with establishment of contacts between floating thyroid cancer cells and formation of multi-cellular spheroids. This process was associated with activation of gap junctional transfer. Increased expression of the gap junction molecule Connexin43 was found in papillary and anaplastic cancer cells forming spheroids. All non-adherent cancer cells showed a lower proliferation rate compared with adherent cells but were more resistant to serum deprivation. AKT was constitutively activated in cancer cells forming spheroids. Inhibition of gap junctional transfer through Connexin43 silencing, or by treatment with the gap junction disruptor carbenoxolone, resulted in loss of pAKT and induction of apoptosis in a cell-type-specific manner. In human thyroid tissue, cancer cells that had infiltrated blood vessels showed morphological similarity to cancer cells forming spheroids in vitro. Intra-vascular cancer cells demonstrated prominent AKT activation in papillary and follicular cancers. Increased Connexin43 immunoreactivity was observed only in intra-vascular papillary cancer cells. Our data demonstrate that establishment of inter-cellular communication contributes to thyroid cancer cell resistance to anoikis. These findings suggest that disruption of gap junctional transfer could represent a potential therapeutic strategy for prevention of metastases.

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RAPID COMMUNICATION: Predominant Intracellular Overexpression of the Na+/I− Symporter (NIS) in a Large Sampling of Thyroid Cancer Cases

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.6.7746 ◽

2001 ◽

Vol 86 (6) ◽

pp. 2697-2700 ◽

Cited By ~ 1

Author(s):

Orsolya Dohán ◽

Zubair Baloch ◽

Zsuzsa Bánrévi ◽

Virginia Livolsi ◽

Nancy Carrasco

Keyword(s):

Plasma Membrane ◽

Thyroid Cancer ◽

Protein Expression ◽

Cancer Cells ◽

Malignant Transformation ◽

Thyroid Tissue ◽

Rapid Communication ◽

High Affinity ◽

Intracellular Compartments ◽

Thyroid Cancer Cells

ABSTRACT Here we report the analysis of the Na+/I− symporter (NIS) protein expression in 57 thyroid cancer samples by immunohistochemistry with high-affinity anti-NIS Abs. As many as 70% of these samples exhibited increased NIS expression with respect to the normal surrounding thyroid tissue. Most significantly, NIS was located in these samples either in both the plasma membrane and intracellular compartments simultaneously, or exclusively in intracellular compartments. This suggests that NIS is clearly expressed or even overexpressed in most thyroid cancer cells, but malignant transformation in some of these cells interferes either with the proper targeting of NIS to the plasma membrane, or with the mechanisms that retain NIS in the plasma membrane after it has been targeted. The results further indicate that, in addition to indicating NIS expression in cases where it is absent (∼30%), improvements in 131I radioablation therapy might result from promoting targeting of NIS to the plasma membrane in the majority (∼70%) of thyroid cancers.

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Cooperative effects of SAHA and VPA on NIS gene expression and proliferation of thyroid cancer cells

Journal of Molecular Endocrinology ◽

10.1530/jme-11-0063 ◽

2012 ◽

Vol 48 (3) ◽

pp. 217-227 ◽

Cited By ~ 9

Author(s):

Cinzia Puppin ◽

Nadia Passon ◽

Jerome M Hershman ◽

Sebastiano Filetti ◽

Stefania Bulotta ◽

...

Keyword(s):

Gene Expression ◽

Thyroid Cancer ◽

Cancer Cells ◽

Histone Deacetylase Inhibitors ◽

Synergistic Effects ◽

Trichostatin A ◽

Target Sequence ◽

Epigenetic Mechanisms ◽

Sodium Iodide Symporter ◽

Thyroid Cancer Cells

Histone deacetylase inhibitors (HDACi) have shown both anti-proliferative and redifferentiating effects in thyroid cancer cells. Also, they induce the expression of the sodium–iodide symporter gene (NIS(SLC5A5)), a crucial step for radioiodine treatment of thyroid malignancies. Here we investigated the effects of suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA) on BCPAP and FRO thyroid cancer cells, extending our analysis on the epigenetic mechanisms underlying theNISgene expression stimulation. In both cell lines we found a cooperative effect of the two compounds on either cell viability andNISgene expression, resulting in acquired/increased ability to uptake the radioiodine. Such effect was specific since it was not observed for expression of other genes or when SAHA was used in combination with trichostatin A. By using chromatin immunoprecipitation, we investigated epigenetic mechanisms underlying SAHA and VPA effects. Cooperation among the two HDACi occurred on H3 histone trimethylation at lysine 4 (H3K4me3) and not on histone acetylation. However, effects on H3K4me3 were detected only at the level of NIS Proximal Basal Promoter (NIS-PBP) in FRO cells and only at the level of NIS Upstream Enhancer (NIS-NUE) in BCPAP cells. Our data indicate that epigenetic changes are involved in the synergistic effects of VPA and SAHA onNISgene expression and that the cellular context modifies effects of HDACi in terms of H3K4me3 target sequence. Investigation of cooperation among different HDACi may provide clues for better defining their mechanism of action in view of their use in thyroid cancer treatment.

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