scholarly journals Notch Signaling Is Involved in Expression of Thyrocyte Differentiation Markers and Is Down-Regulated in Thyroid Tumors

2008 ◽  
Vol 93 (10) ◽  
pp. 4080-4087 ◽  
Author(s):  
E. Ferretti ◽  
E. Tosi ◽  
A. Po ◽  
A. Scipioni ◽  
R. Morisi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Cancer ◽  
Notch Signaling ◽  
Notch Pathway ◽  
Human Thyroid ◽  
Thyroid Tumors ◽  
Follicular Cells ◽  
Differentiation Markers ◽  
Thyroid Follicular Cells ◽  
Thyroid Cancer Cells

Context: Notch genes encode receptors for a signaling pathway that regulates cell growth and differentiation in various contexts, but the role of Notch signaling in thyroid follicular cells has never been fully published. Objective: The objective of the study was to characterize the expression of Notch pathway components in thyroid follicular cells and Notch signaling activities in normal and transformed thyrocytes. Design/Setting and Patients: Expression of Notch pathway components and key markers of thyrocyte differentiation was analyzed in murine and human thyroid tissues (normal and tumoral) by quantitative RT-PCR and immunohistochemistry. The effects of Notch overexpression in human thyroid cancer cells and FTRL-5 cells were explored with analysis of gene expression, proliferation assays, and experiments involving transfection of a luciferase reporter construct containing human NIS promoter regions. Results: Notch receptors are expressed during the development of murine thyrocytes, and their expression levels parallel those of thyroid differentiation markers. Notch signaling characterized also normal adult thyrocytes and is regulated by TSH. Notch pathway components are variably expressed in human normal thyroid tissue and thyroid tumors, but expression levels are clearly reduced in undifferentiated tumors. Overexpression of Notch-1 in thyroid cancer cells restores differentiation, reduces cell growth rates, and stimulates NIS expression via a direct action on the NIS promoter. Conclusion: Notch signaling is involved in the determination of thyroid cell fate and is a direct regulator of thyroid-specific gene expression. Its deregulation may contribute to the loss of differentiation associated with thyroid tumorigenesis.

Gene Expression of Differentiation Markers in Xenotransplanted Human Thyroid Tumors of Nude Rats1

1996 ◽  
pp. 105-107
Author(s):  
C. Hoang-Vu ◽  
H. Leitolf ◽  
G. F. W. Scheumann ◽  
H. Dralle ◽  
A. von zur Mühlen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Thyroid ◽  
Thyroid Tumors ◽  
Differentiation Markers

scholarly journals Thyroglobulin Suppresses Thyroid-Specific Gene Expression in Cultures of Normal But Not Neoplastic Human Thyroid Follicular Cells

2014 ◽  
Vol 99 (4) ◽  
pp. E694-E702 ◽  
Author(s):  
Yuko Ishido ◽  
Kazuko Yamazaki ◽  
Makoto Kammori ◽  
Yoshiyuki Sugishita ◽  
Yuqian Luo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Thyroid ◽  
Specific Gene ◽  
Follicular Cells ◽  
Specific Gene Expression ◽  
Thyroid Follicular Cells

Valproic acid inhibits growth, induces apoptosis, and modulates apoptosis-regulatory and differentiation gene expression in human thyroid cancer cells

Surgery ◽  
2005 ◽  
Vol 138 (6) ◽  
pp. 979-985 ◽  
Author(s):  
Wen T. Shen ◽  
Ted S. Wong ◽  
Woong-Youn Chung ◽  
Mariwil G. Wong ◽  
Electron Kebebew ◽  
...  
Keyword(s):  
Gene Expression ◽  
Valproic Acid ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
Human Thyroid ◽  
Differentiation Gene ◽  
Thyroid Cancer Cells

Anti-proliferative effects of evodiamine on human thyroid cancer cells

2014 ◽  
Author(s):  
Ying-Ray Lee ◽  
Chieh-Hsiang Lu ◽  
Yi-Sheng Chang ◽  
Yi-Wen Liu
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Human Thyroid ◽  
Thyroid Cancer Cells

scholarly journals Changes in Exosome Release in Thyroid Cancer Cells after Prolonged Exposure to Real Microgravity in Space

2021 ◽  
Vol 22 (4) ◽  
pp. 2132
Author(s):  
Petra M. Wise ◽  
Paolo Neviani ◽  
Stefan Riwaldt ◽  
Thomas Juhl Corydon ◽  
Markus Wehland ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Prolonged Exposure ◽  
Space Station ◽  
Surface Protein ◽  
Surface Expression ◽  
Human Thyroid ◽  
Gene And Protein Expression ◽  
Thyroid Cancer Cells

Space travel has always been the man’s ultimate destination. With the ability of spaceflight though, came the realization that exposure to microgravity has lasting effects on the human body. To counteract these, many studies were and are undertaken, on multiple levels. Changes in cell growth, gene, and protein expression have been described in different models on Earth and in space. Extracellular vesicles, and in particular exosomes, are important cell-cell communicators, being secreted from almost all the cells and therefore, are a perfect target to further investigate the underlying reasons of the organism’s adaptations to microgravity. Here, we studied supernatants harvested from the CellBox-1 experiment, which featured human thyroid cancer cells flown to the International Space Station during the SpaceX CRS-3 cargo mission. The initial results show differences in the number of secreted exosomes, as well as in the distribution of subpopulations in regards to their surface protein expression. Notably, alteration of their population regarding the tetraspanin surface expression was observed. This is a promising step into a new area of microgravity research and will potentially lead to the discovery of new biomarkers and pathways of cellular cross-talk.

scholarly journals The RET Kinase Inhibitor NVP-AST487 Blocks Growth and Calcitonin Gene Expression through Distinct Mechanisms in Medullary Thyroid Cancer Cells

2007 ◽  
Vol 67 (14) ◽  
pp. 6956-6964 ◽  
Author(s):  
Nagako Akeno-Stuart ◽  
Michelle Croyle ◽  
Jeffrey A. Knauf ◽  
Roberta Malaguarnera ◽  
Donata Vitagliano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Medullary Thyroid ◽  
Calcitonin Gene ◽  
Thyroid Cancer Cells

scholarly journals Protein Kinase A-Independent Inhibition of Proliferation and Induction of Apoptosis in Human Thyroid Cancer Cells by 8-Cl-Adenosine

2008 ◽  
Vol 93 (3) ◽  
pp. 1020-1029 ◽  
Author(s):  
Audrey J. Robinson-White ◽  
Hui-Pin Hsiao ◽  
Wolfgang W. Leitner ◽  
Elizabeth Greene ◽  
Andrew Bauer ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Cancer Cells ◽  
Human Thyroid ◽  
Inhibition Of Proliferation ◽  
Thyroid Cancer Cells ◽  
Kinase A

Abstract Purpose: Protein kinase A (PKA) affects cell proliferation in many cell types and is a potential target for cancer treatment. PKA activity is stimulated by cAMP and cAMP analogs. One such substance, 8-Cl-cAMP, and its metabolite 8-Cl-adenosine (8-Cl-ADO) are known inhibitors of cancer cell proliferation; however, their mechanism of action is controversial. We have investigated the antiproliferative effects of 8-Cl-cAMP and 8-CL-ADO on human thyroid cancer cells and determined PKA’s involvement. Experimental Design: We employed proliferation and apoptosis assays and PKA activity and cell cycle analysis to understand the effect of 8-Cl-ADO and 8-Cl-cAMP on human thyroid cancer and HeLa cell lines. Results: 8-Cl-ADO inhibited proliferation of all cells, an effect that lasted for at least 4 d. Proliferation was also inhibited by 8-Cl-cAMP, but this inhibition was reduced by 3-isobutyl-1-methylxanthine; both drugs stimulated apoptosis, and 3-isobutyl-1-methylxanthine drastically reduced 8-Cl-cAMP-induced cell death. 8-Cl-ADO induced cell accumulation in G1/S or G2/M cell cycle phases and differentially altered PKA activity and subunit levels. PKA stimulation or inhibition and adenosine receptor agonists or antagonists did not significantly affect proliferation. Conclusions: 8-Cl-ADO and 8-Cl-cAMP inhibit proliferation, induce cell cycle phase accumulation, and stimulate apoptosis in thyroid cancer cells. The effect of 8-Cl-cAMP is likely due to its metabolite 8-Cl-ADO, and PKA does not appear to have direct involvement in the inhibition of proliferation by 8-Cl-ADO. 8-Cl-ADO may be a useful therapeutic agent to be explored in aggressive thyroid cancer.

scholarly journals Mining Prognostic Significance Genes in Human Thyroid Cancer Using Bioinformatics Analysis

2021 ◽  
Author(s):  
Hui Zhao ◽  
Pengjie Li ◽  
Junjian Li ◽  
Lian Duan ◽  
Yanzhu Jiao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Thyroid Cancer ◽  
Function Analysis ◽  
Akt Signaling ◽  
Differentially Expressed ◽  
Human Thyroid ◽  
Marker Genes ◽  
Clinical Prognosis ◽  
Mesenchymal Transition

Abstract Background Thyroid carcinoma (THC) is very common, yet its pathogenesis and the key tumor marker genes remain unclear.Methods Gene expression datasets from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas Project (TCGA) were used for gene differential expression analysis. Functional annotation analysis, Clinical prognosis analysis and Differential DNA methylation analysis were conducted on the differentially expressed genes (DEGs). Results Compared with induced pluripotent stem cells (iPSCs), 237 differentially expressed THC intersection genes derived from GEO and TCGA were obtained, of which 153 genes were closely related to clinicopathological features and prognostic effects. Biological function analysis indicated that most of these DEGs were involved in the proteinaceous extracellular matrix, epithelial-to-mesenchymal transition (EMT), and PI3K-Akt signaling pathway, resulting in effects on tumor invasion and metastasis. Finally, the results of differential methylation levels demonstrated that the high expression of 4 genes (CHI3L1, NFE2L3, S100A2, and LAMB3) was strongly correlated with the development of thyroid cancer.Conclusions Proteinaceous extracellular matrix, EMT, and PI3K-Akt signaling pathways were of great significance in the metastasis and invasion of THC. Genes such as CHI3L1, NFE2L3, S100A2, and LAMB3 were susceptible to THC.

scholarly journals DDR1 regulates thyroid cancer cell differentiation via IGF-2/IR-A autocrine signaling loop

2019 ◽  
Vol 26 (1) ◽  
pp. 197-214 ◽  
Author(s):  
Veronica Vella ◽  
Maria Luisa Nicolosi ◽  
Patrizia Cantafio ◽  
Michele Massimino ◽  
Rosamaria Lappano ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Differentiation ◽  
Epithelial To Mesenchymal Transition ◽  
Human Thyroid ◽  
Autocrine Signaling ◽  
Differentiation Markers ◽  
Autocrine Loop ◽  
Mesenchymal Transition ◽  
Poorly Differentiated ◽  
Induced Changes

Patients with thyroid cancers refractory to radioiodine (RAI) treatment show a limited response to various therapeutic options and a low survival rate. The recent use of multikinase inhibitors has also met limited success. An alternative approach relies on drugs that induce cell differentiation, as the ensuing increased expression of the cotransporter for sodium and iodine (NIS) may partially restore sensitivity to radioiodine. The inhibition of the ERK1/2 pathway has shown some efficacy in this context. Aggressive thyroid tumors overexpress the isoform-A of the insulin receptor (IR-A) and its ligand IGF-2; this IGF-2/IR-A loop is associated with de-differentiation and stem-like phenotype, resembling RAI-refractory tumors. Importantly, IR-A has been shown to be positively modulated by the non-integrin collagen receptor DDR1 in human breast cancer. Using undifferentiated human thyroid cancer cells, we now evaluated the effects of DDR1 on IGF-2/IR-A loop and on markers of cell differentiation and stemness. DDR1 silencing or downregulation caused significant reduction of IR-A and IGF-2 expression, and concomitant increased levels of differentiation markers (NIS, Tg, TSH, TPO). Conversely, markers of epithelial-to-mesenchymal transition (Vimentin, Snail-2, Zeb1, Zeb2 and N-Cadherin) and stemness (OCT-4, SOX-2, ABCG2 and Nanog) decreased. These effects were collagen independent. In contrast, overexpression of either DDR1 or its kinase-inactive variant K618A DDR1-induced changes suggestive of less differentiated and stem-like phenotype. Collagen stimulation was uneffective. In conclusion, in poorly differentiated thyroid cancer, DDR1 silencing or downregulation blocks the IGF-2/IR-A autocrine loop and induces cellular differentiation. These results may open novel therapeutic approaches for thyroid cancer.

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