scholarly journals Aurora B Overexpression Associates with the Thyroid Carcinoma Undifferentiated Phenotype and Is Required for Thyroid Carcinoma Cell Proliferation

2005 ◽  
Vol 90 (2) ◽  
pp. 928-935 ◽  
Author(s):  
Rosanna Sorrentino ◽  
Silvana Libertini ◽  
Pier Lorenzo Pallante ◽  
Giancarlo Troncone ◽  
Lucio Palombini ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Critical Role ◽  
Thyroid Tissue ◽  
Immunohistochemical Analysis ◽  
Aurora Kinase ◽  
Anaplastic Carcinoma ◽  
Human Thyroid ◽  
Pcr Analysis ◽  
Aurora B ◽  
Thyroid Carcinomas

Alterations in chromosome number (aneuploidy) are common in human neoplasias. Loss of mitotic regulation is believed to induce aneuploidy in cancer cells and act as a driving force during the malignant progression. The serine/theronine protein kinases of aurora family genes play a critical role in the regulation of key cell cycle processes. Aurora B mediates chromosome segregation by ensuring orientation of sister chromatids and overexpression of Aurora B in diploid human cells NHDF (normal human diploid fibroblast) induces multinuclearity. We analyzed Aurora B expression in human thyroid carcinomas. Cell lines originating from different histotypes showed an increase in Aurora B expression. Immunohistochemical analysis of archive samples showed a high expression of Aurora B in anaplastic thyroid carcinomas; conversely, Aurora B expression was not detectable in normal thyroid tissue. Real-time PCR analysis confirmed a strong expression of Aurora B in anaplastic thyroid carcinomas. The block of Aurora B expression induced by RNA interference or by using an inhibitor of Aurora kinase activity significantly reduced the growth of thyroid anaplastic carcinoma cells.

scholarly journals Deregulation of microRNA expression in follicular cell-derived human thyroid carcinomas

2010 ◽  
Vol 17 (1) ◽  
pp. F91-F104 ◽  
Author(s):  
Pierlorenzo Pallante ◽  
Rosa Visone ◽  
Carlo Maria Croce ◽  
Alfredo Fusco
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Thyroid Tissue ◽  
Endocrine System ◽  
Follicular Carcinoma ◽  
Thyroid Neoplasms ◽  
Anaplastic Thyroid Cancer ◽  
Microrna Expression ◽  
Human Thyroid ◽  
Thyroid Carcinomas

Carcinoma of the thyroid gland is an uncommon cancer, but one of the most frequent malignancies of the endocrine system. Most thyroid cancers are derived from the follicular cells. Follicular carcinoma is considered more malignant than papillary thyroid carcinoma (PTC), and anaplastic thyroid cancer (ATC) is one of the most lethal human cancers. Even though several genetic lesions have been already described in human thyroid cancer, particularly in the papillary histotype, the mechanisms underlying the development of these neoplasias are still far from being completely elucidated. Some years ago, several studies were undertaken to analyze the expression of microRNAs (miRNAs or miRs) in thyroid carcinoma to evaluate a possible role of their deregulation in the process of carcinogenesis. These studies showed an aberrant microRNA expression profile that distinguishes unequivocally among PTC, ATC, and normal thyroid tissue. Here, other than summarizing the current findings on microRNA expression in human thyroid carcinomas, we discuss the mechanisms by which microRNA deregulation may play a role in thyroid carcinogenesis, and the possible use of microRNA knowledge in the diagnosis and therapy of thyroid neoplasms.

scholarly journals Differential roles of RET isoforms in medullary and papillary thyroid carcinomas

2017 ◽  
Vol 24 (1) ◽  
pp. 53-69 ◽  
Author(s):  
Eric Y Lian ◽  
Sarah M Maritan ◽  
Jessica G Cockburn ◽  
Katayoon Kasaian ◽  
Mathieu J F Crupi ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Cell Survival ◽  
Tumour Progression ◽  
Carcinoma Cells ◽  
Protein Isoforms ◽  
Human Thyroid ◽  
Papillary Thyroid ◽  
Anoikis Resistance ◽  
Thyroid Carcinomas ◽  
And Migration

The RET receptor tyrosine kinase mediates cell proliferation, survival and migration in embryogenesis and is implicated in the transformation and tumour progression in multiple cancers. RET is frequently mutated and constitutively activated in familial and sporadic thyroid carcinomas. As a result of alternative splicing, RET is expressed as two protein isoforms, RET9 and RET51, which differ in their unique C-terminal amino acids. These isoforms have distinct intracellular trafficking and associated signalling complexes, but functional differences are not well defined. We used shRNA-mediated knockdown (KD) of individual RET isoforms or of total RET to evaluate their functional contributions in thyroid carcinoma cells. We showed that RET is required for cell survival in medullary (MTC) but not papillary thyroid carcinoma (PTC) cells. In PTC cells, RET depletion reduced cell migration and induced a flattened epithelial-like morphology. RET KD decreased the expression of mesenchymal markers and matrix metalloproteinases and reduced anoikis resistance and invasive potential. Further, we showed that RET51 depletion had significantly greater effects on each of these processes than RET9 depletion in both MTC and PTC cells. Finally, we showed that expression of RET, particularly RET51, was correlated with malignancy in a panel of human thyroid tumour tissues. Together, our data show that RET expression promotes a more mesenchymal phenotype with reduced cell–cell adhesion and increased invasiveness in PTC cell models, but is more important for tumour cell survival, proliferation and anoikis resistance in MTC models. Our data suggest that the RET51 isoform plays a more prominent role in mediating these processes compared to RET9.

Immunohistochemical Analysis of Estrogen Receptors in 313 Paraffin Section Cases of Human Thyroid Tissue

Oncology ◽  
1993 ◽  
Vol 50 (2) ◽  
pp. 132-136 ◽  
Author(s):  
Yoshio Hiasa ◽  
Hiroto Nishioka ◽  
Yoshiteru Kitahori ◽  
Katsunari Yane ◽  
Shingo Nakaoka ◽  
...  
Keyword(s):  
Estrogen Receptors ◽  
Thyroid Tissue ◽  
Paraffin Section ◽  
Immunohistochemical Analysis ◽  
Human Thyroid ◽  
Human Thyroid Tissue

Thyrotrophin receptors in normal and neoplastic (primary and metastatic) canine thyroid tissue

1992 ◽  
Vol 132 (3) ◽  
pp. 461-468 ◽  
Author(s):  
C. P. Verschueren ◽  
G. R. Rutteman ◽  
J. H. Vos ◽  
J. E. Van Dijk ◽  
T. W. A. de Bruin
Keyword(s):  
Thyroid Carcinoma ◽  
Binding Affinity ◽  
Receptor Binding ◽  
Binding Sites ◽  
Thyroid Tissue ◽  
Thyroid Neoplasms ◽  
Tsh Receptor ◽  
Normal Thyroid ◽  
Thyroid Carcinomas ◽  
Receptor Number

ABSTRACT Thyrotrophin (TSH) is the conditional growth factor of thyroid epithelial cells. Abnormalities in TSH-receptor binding such as a low receptor number or low binding affinity may be a marker of thyroid carcinoma or metastases, or may exhibit a relationship with the functional variability of such tissues. The dog was used as a model to characterize TSH-receptor binding in normal thyroid tissues, naturally occurring thyroid neoplasms and distant metastases. In normal dog thyroid tissues, specific 125I-labelled TSH binding ranged from 2·7 to 15·5%, and low cross-reactivity with bovine LH (0·023%) was observed. One class of TSH-binding sites was found in eight normal thyroid tissues and 22 thyroid carcinomas; two normal thyroid tissues and one tumour exhibited two classes of binding sites. The concentration of binding sites was lower in the five carcinomas with reduced pertechnetate uptake (0·09 pmol/mg protein) than in the five thyroid neoplasms with increased uptake (0·19 pmol/mg) (P= 0·055). Compared with the original carcinoma tissues, TSH binding revealed a reduced binding affinity in eight out of eleven metastases. Two metastases showed a complete absence of TSH binding, suggesting that they were not dependent on TSH for growth. We conclude that one class of TSH-binding site is predominant in normal dog thyroid tissues and dog thyroid carcinomas. TSH could therefore contribute, at least in theory, to further growth of primary dog thyroid carcinomas. Secondly, assays measuring TSH binding may not be able to discriminate between malignant and benign dog thyroid tumours. TSH receptor number or affinity may be related to the functional variability of thyroid neoplasms. The absence of TSH binding in some metastases demonstrated that this characteristic can be acquired during the natural history of a differentiated thyroid carcinoma. Journal of Endocrinology (1992) 132, 461–468

Radioimmunoscintigraphy with Anti-Thyroglobulin Monoclonal Antibodies

1986 ◽  
Vol 25 (06) ◽  
pp. 232-234 ◽  
Author(s):  
U. J. Hoffmann ◽  
W. Köhnlein ◽  
D. Skutta ◽  
M. Fischer
Keyword(s):  
Monoclonal Antibodies ◽  
Thyroid Carcinoma ◽  
Nude Mice ◽  
Human Thyroid ◽  
Imaging Studies ◽  
Thyroid Carcinomas ◽  
Significant Uptake ◽  
Undifferentiated Thyroid Carcinoma ◽  
Monoclonal Mouse

Monoclonal mouse antibodies to human thyroglobulin were conjugated to the cyclic dianhydride of DTPA. After radiolabelling with 111 In this compound was injected into nude mice bearing various human thyroid carcinomas. Repeated imaging studies were carried out 15 min to 50 h after tracer administration. In both papillary and undifferentiated thyroid carcinoma no significant uptake of radiolabeled anti-hTG-MAb was observed.

scholarly journals Novel Isoforms of Periostin Expressed in the Human Thyroid

2010 ◽  
Vol 1 ◽  
pp. JCM.S5899 ◽  
Author(s):  
Yanhua Bai ◽  
Misa Nakamura ◽  
Gengyin Zhou ◽  
Yaqiong Li ◽  
Zhiyan Liu ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Matrix Protein ◽  
Thyroid Tissue ◽  
Anaplastic Thyroid Carcinoma ◽  
Extracellular Matrix Protein ◽  
Human Thyroid ◽  
Tissue Samples ◽  
C Terminus ◽  
Novel Isoforms

Periostin is an extracellular matrix protein. Five isoforms of human periostin cDNA have been reported, but the expression of periostin isoforms in the human thyroid tissue is by far unknown. A group of primer sets were designed to amplify the full length of cDNA sequence of periostin. Using human thyroid carcinoma and their paired non-neoplastic tissues together with anaplastic thyroid carcinoma cell lines, we examined the presence of periostin cDNA isoforms by RT-PCR and direct DNA sequence analysis. We identified eight coexisting cDNA isoforms in all the tissue samples and cell lines. Three of them were unique to this study. Especially two of them haven't been previously reported in any species. The eight periostin isoforms differ in the C-terminus from exon XII to exon XXI where alternative splicing usually happens. This is the first report that demonstrates all the eight isoforms of periostin cDNA expressed in the human thyroid gland and identifies three novel isoforms.

PROTEINS OF NORMAL AND PATHOLOGICAL HUMAN THYROID TISSUE

1964 ◽  
Vol 45 (2) ◽  
pp. 161-170 ◽  
Author(s):  
P. G. Stanley
Keyword(s):  
Correlation Coefficient ◽  
Ammonium Sulphate ◽  
Analytical Ultracentrifugation ◽  
Thyroid Tissue ◽  
Paper Electrophoresis ◽  
Anaplastic Carcinoma ◽  
T Test ◽  
Human Thyroid ◽  
Salting Out ◽  
Simplified Procedure

ABSTRACT Salting-out curves, analytical ultracentrifugation and paper electrophoresis were used to examine saline extracts of 21 human thyroid glands or portions of glands, both normal and pathological. A simplified procedure of plotting salting-out curves was used. The glands could be divided into 2 groups, the first characterized by a high proportion of protein sedimenting with S20,w 18–20 (55–75 %) and a low proportion of protein sedimenting with S20,w 4 (20–40%), the second characterized by a low proportion of protein sedimenting with S20,w 18–20 (20–55%) and a high proportion of protein sedimenting with S20,w 4 (45–75%). Group 1 comprises normal glands, multinodular goitres, a follicular-alveolar carcinoma and an anaplastic carcinoma containing much follicular tissue; group 2 comprises a follicular and trabecular adenoma, a follicularpapillary carcinoma, anaplastic carcinomata and toxic goitres. Protein sedimenting with S20,w 18–20 could be correlated with protein salting out between 35 and 45% saturation with ammonium sulphate (21 points, correlation coefficient 0.931, P < 0.001 by t test) and there was some correlation between protein sedimenting with S20,w 4 and protein salting out between 20 and 30 % saturation with ammonium sulphate provided some points were omitted (18 points, correlation coefficient 0.600, P < 0.01 by t test). It is suggested that the protein salting out between 20 and 30 % saturation is a nucleoprotein.

scholarly journals Differential regulation of monocarboxylate transporter 8 expression in thyroid cancer and hyperthyroidism

2017 ◽  
Vol 177 (3) ◽  
pp. 243-250 ◽  
Author(s):  
Julia Badziong ◽  
Saskia Ting ◽  
Sarah Synoracki ◽  
Vera Tiedje ◽  
Klaudia Brix ◽  
...  
Keyword(s):  
Amino Acid ◽  
Thyroid Carcinoma ◽  
Thyroid Tissue ◽  
Follicular Adenoma ◽  
Monocarboxylate Transporter ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Amino Acid Transporters ◽  
Variable Expression

Objective Thyroid hormone (TH) transporters are expressed in thyrocytes and most play a role in TH release. We asked whether expression of the monocarboxylate transporter 8 (MCT8) and the L-type amino acid transporters LAT2 and LAT4 is changed with thyrocyte dedifferentiation and in hyperfunctioning thyroid tissues. Design and methods Protein expression and localization of transporters was determined by immunohistochemistry in human thyroid specimen including normal thyroid tissue (NT, n = 19), follicular adenoma (FA, n = 44), follicular thyroid carcinoma (FTC, n = 45), papillary thyroid carcinoma (PTC, n = 40), anaplastic thyroid carcinoma (ATC, n = 40) and Graves’ disease (GD, n = 50) by calculating the ‘hybrid’ (H) score. Regulation of transporter expression was investigated in the rat follicular thyroid cell line PCCL3 under basal and thyroid stimulating hormone (TSH) conditions. Results MCT8 and LAT4 were localized at the plasma membrane, while LAT2 transporter showed cytoplasmic localization. MCT8 expression was downregulated in benign and malignant thyroid tumours as compared to NT. In contrast, significant upregulation of MCT8, LAT2 and LAT4 was found in GD. Furthermore, a stronger expression of MCT8 was demonstrated in PCCL3 cells after TSH stimulation. Conclusions Downregulation of MCT8 in thyroid cancers qualifies MCT8 as a marker of thyroid differentiation. The more variable expression of LATs in distinct thyroid malignancies may be linked with other transporter properties relevant to altered metabolism in cancer cells, i.e. amino acid transport. Consistent upregulation of MCT8 in GD is in line with increased TH release in hyperthyroidism, an assumption supported by our in vitro results showing TSH-dependent upregulation of MCT8.

scholarly journals Expression of RET and its ligand complexes, GDNF/GFRalpha-1 and NTN/GFRalpha-2, in medullary thyroid carcinomas

2000 ◽  
pp. 643-649 ◽  
Author(s):  
T Frisk ◽  
F Farnebo ◽  
J Zedenius ◽  
L Grimelius ◽  
A Hoog ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Thyroid Tissue ◽  
Pcr Analysis ◽  
Medullary Thyroid ◽  
Thyroid Carcinomas ◽  
Reverse Transcription Pcr ◽  
Membrane Bound ◽  
Tissue Specimens ◽  
High Level ◽  
Medullary Thyroid Carcinomas

OBJECTIVE: Mutations in the RET proto-oncogene are found in about one third of sporadic medullary thyroid carcinomas (MTCs), mostly affecting codon 918. Glial cell line derived neurotropic factor (GDNF) and its membrane-bound GDNF family receptor alpha (GFRalpha-1), as well as neurturin (NTN) and its membrane-bound receptor GFRalpha-2 form a complex with the RET product, a receptor tyrosine kinase, resulting in downstream signaling to the nucleus. DESIGN: To elucidate the role of these RET ligands in MTC tumorigenesis, their expression was determined in 15 MTC samples, one papillary thyroid carcinoma (PTC) and three normal thyroid tissue specimens. METHODS: The mRNA expression of RET, GDNF, GFRalpha-1, NTN and GFRalpha-2 was investigated by mRNA in situ hybridization, and confirmed by reverse transcription-PCR analysis. RESULTS: None of the five genes was expressed in the normal thyroids or in the PTC. All MTCs showed expression of RET, 13 expressed GDNF, 12 expressed GFRalpha-1 and 9 expressed NTN and GFRalpha-2. In 7 of the tumors RET, GDNF and GFRalpha-1 were expressed at high levels, and in five of these seven tumors NTN and GFRalpha-2 genes were also expressed at high levels. The high level of expression was preferentially seen in tumor cells adjacent to stroma and connective tissue. All MTCs without expression of the RET ligands harbored the RET codon 918 mutation. CONCLUSIONS: The results suggest that this signaling pathway is important for MTC development, and that it may be activated by expression of the RET ligand complexes by the tumor cells themselves.

scholarly journals A Morphometric Analysis of Nucleoli in Cultured Carcinoma Cells of the Human Thyroid

1998 ◽  
Vol 16 (3) ◽  
pp. 131-140 ◽  
Author(s):  
Lars Andersen ◽  
Lars Kayser ◽  
Niels Keiding ◽  
Jens Thomsen
Keyword(s):  
Epithelial Cells ◽  
Thyroid Carcinoma ◽  
Thyroid Tissue ◽  
Microscopic Level ◽  
Carcinoma Cells ◽  
Electron Microscopic Level ◽  
Human Thyroid ◽  
Electron Microscopic ◽  
Normal Thyroid ◽  
Granular Component

Cells from 7 patients operated on for thyroid cancer were investigated. Samples of cells from the carcinoma and from the normal thyroid tissue were cultured with and without TSH stimulation. For light microscopy, serial sections of cells were cut and the size of nucleoli was measured and the number of nucleoli per cell counted. At the electron microscopic level the number and the volume of the fibrillar centres (FC) were estimated taking the Swiss cheese effect into account. The areal densities of FC, the fibrillar and granular component in nucleoli were determined by point counting. The results indicate that the malignant transformation has no influence on the size of the FC, but the observed numbers as well as the total area of FC are larger in cancer cells than in the normal thyroid epithelial cells. The nucleolar density of the fibrillar component is larger and that of the granular component is smaller in thyroid carcinoma cells than in non‐malignant thyroid epithelial cells (p= 0.0001). Thus simple morphometry at the electron microscopic level might be helpful to discriminate between thyroid epithelial cells and thyroid carcinoma cells in culture.

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