scholarly journals Steroid receptor coactivator-1 interacts with NF-κB to increase VEGFC levels in human thyroid cancer

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Bo Gao ◽  
Lingji Guo ◽  
Donglin Luo ◽  
Yan Jiang ◽  
Jianjie Zhao ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Tissue ◽  
Lymphatic Vessels ◽  
Steroid Receptor ◽  
Human Thyroid ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid ◽  
Steroid Receptor Coactivator ◽  
Lymphatic Metastases ◽  
Factor C

Thyroid cancer is the most common endocrine cancer, and has a high incidence of lymphatic metastasis. Vascular endothelial growth factor C (VEGFC) is essential for development of lymphatic vessels and lymphatic metastases during carcinogenesis. Steroid receptor coactivator-1 (SRC-1) interacts with nuclear receptors and transcription factors to promote tumor proliferation and metastasis. However, the correlation between SRC-1 and VEGFC levels in the lymphatic metastases of thyroid cancer remains unclear. We analyzed 20-paired specimens of thyroid cancer tissue and normal thyroid tissue and found increased levels of SRC-1 and VEGFC proteins in 13/20 and 15/20 thyroid cancer specimens, respectively, when compared with those levels in specimens of normal thyroid tissue. A high level of SRC-1 expression was positively correlated with VEGFC and lymphatic endothelial cell marker LYVE-1 expression. Papillary thyroid carcinoma cell line TPC-1 displayed high levels of SRC-1 and VEGFC expression and was selected for stable knockdown of SRC-1 in vitro. Inhibition of SRC-1 significantly reduced the VEGFC levels in TPC-1 cells. We found that SRC-1 binds to transcription factor NF-kB (p50/p65), and that this coactivation complex directly promoted VEGFC transcription, which could be abrogated by SRC-1 knockdown. Up-regulated NF-kB signaling was also confirmed in thyroid cancer tissues. In vivo studies showed that SRC-1 knockdown restricted tumor growth, reduced the numbers of LYVE-1-positive lymphatic vessels, and decreased the levels of VEGFC in tumor tissues. These results suggest a tumorigenic role for SRC-1 in thyroid cancer via its ability to regulate VEGFC expression.

scholarly journals Intracellular expression of reactive oxygen species-generating NADPH oxidase NOX4 in normal and cancer thyroid tissues

2010 ◽  
Vol 17 (1) ◽  
pp. 27-37 ◽  
Author(s):  
Urbain Weyemi ◽  
Bernard Caillou ◽  
Monique Talbot ◽  
Rabii Ameziane-El-Hassani ◽  
Ludovic Lacroix ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Biological Effects ◽  
Thyroid Tissue ◽  
Reactive Oxygen ◽  
Human Thyroid ◽  
Oxygen Species ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid ◽  
Cellular Expression

NADPH oxidase 4 (NOX4) belongs to the NOX family that generates reactive oxygen species (ROS). Function and tissue distribution of NOX4 have not yet been entirely clarified. To date, in the thyroid gland, only DUOX1/2 NOX systems have been described. NOX4 mRNA expression, as shown by real-time PCR, was present in normal thyroid tissue, regulated by TSH and significantly increased in differentiated cancer tissues. TSH increased the protein level of NOX4 in human thyroid primary culture and NOX4-dependent ROS generation. NOX4 immunostaining was detected in normal and pathologic thyroid tissues. In normal thyroid tissue, staining was heterogeneous and mostly found in activated columnar thyrocytes but absent in quiescent flat cells. Papillary and follicular thyroid carcinomas displayed more homogeneous staining. The p22phox protein that forms a heterodimeric enzyme complex with NOX4 displayed an identical cellular expression pattern and was also positively regulated by TSH. ROS may have various biological effects, depending on the site of production. Intracellular NOX4–p22phox localization suggests a role in cytoplasmic redox signaling, in contrast to the DUOX localization at the apical membrane that corresponds to an extracellular H2O2 production. Increased NOX4–p22phox in cancer might be related to a higher proliferation rate and tumor progression but a role in the development of tumors has to be further studied and established in the future.

Protein composition in single follicles, homogenates and fine-needle aspiration biopsies from normal and diseased human thyroid

1981 ◽  
Vol 96 (3) ◽  
pp. 328-334 ◽  
Author(s):  
B. Anderberg ◽  
S. Eneström ◽  
J. Gillquist ◽  
B. Kägedal ◽  
J. C. Månsson ◽  
...  
Keyword(s):  
Thyroid Tissue ◽  
Protein Composition ◽  
Lithium Therapy ◽  
Protein Fractions ◽  
Human Thyroid ◽  
Lower Amount ◽  
Normal Thyroid Tissue ◽  
Nodular Goitre ◽  
Normal Thyroid ◽  
Thyroid Colloid

Abstract. The protein composition of the thyroid colloid was analysed by microgel electrophoresis and densitometry in 41 euthyroid patients. The colloid samples were obtained from single follicles by micropuncture, from homogenates of microbiopsies or from aspiration biopsies. Fourteen of the patients had morphologically normal thyroid tissue, 18 had atoxic nodular goitre and 9 of the patients had atoxic adenoma. Ten of the patients with nodular goitre had prior to the investigation recieved lithium therapy for psychiatric disorders. The main component of the thyroid colloid was 19S thyroglobulin (TG), but larger iodoproteins (S-TG) and smaller protein fractions, an albumin-like protein and a pre-albumin fraction, were also present in varying relative amounts. Analyses of homogenates of microbiopsies from normal thyroid tissue demonstrated the same protein composition as observed in single follicles. In colloid samples from atoxic nodular goitre the lighter protein fractions were absent in most of the samples. Analyses of homogenates or aspiration biopsies could not demonstrate this alteration in the protein composition in nodular goitre. Lithium therapy resulted in a significantly lower amount of the lighter protein fractions but unchanged amounts of the globulin fractions in atoxic nodular goitre. In the atoxic adenomas the protein composition was heterogeneous. The major globulin fractions as well as the lighter protein fractions were present in the analyses of colloids and homogenates of microbiopsies. Aspiration biopsies from atoxic adenomas could not be used for analyses of the protein composition due to contamination with serum proteins.

Investigation of BK virus, Epstein-Barr virus and human papillomavirus sequences in postoperative thyroid gland specimens

2015 ◽  
Vol 30 (1) ◽  
pp. 104-110 ◽  
Author(s):  
Dimitris Stamatiou ◽  
Stavros P. Derdas ◽  
Emmanouil K. Symvoulakis ◽  
Georgios H. Sakorafas ◽  
Odysseas Zoras ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Epstein Barr Virus ◽  
Thyroid Tissue ◽  
Bk Virus ◽  
Gene Sequences ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid ◽  
Barr Virus ◽  
Epstein Barr ◽  
Tissue Specimens

Background Although recent evidence has implicated viruses in the regulation of epithelial-to-mesenchymal transition and tumor progression, little is known regarding viral infections in thyroid malignancies. Thus the aim of this study was to detect sequences of 3 potentially oncogenic viruses – BK virus (BKV), Epstein-Barr virus (EBV) and human papillomavirus (HPV) – in a series of postoperative thyroid gland specimens. Methods Thirty patients with thyroid nodules who underwent surgery for thyroid disease within a 3-year period were enrolled. Both nodular and adjacent normal thyroid tissue was surgically excised from each patient. Viral gene sequences of BKV (VP1), EBV (LMP1, EBNA2 and EBER1) and HPV were amplified by PCR. The PCR results were confirmed by direct sequencing analysis. Results VP1 gene sequences were detected in 60% (18/30) of thyroid cancer or multinodular hyperplasia lesions compared with in 43.3% (13/30) of adjacent normal thyroid tissue specimens. Fifteen of thirty (50%) of thyroid cancer or multinodular hyperplasia samples revealed LMP1 sequences compared with 46.7% (14/30) of corresponding normal thyroid tissues. EBNA2 gene sequences were detected in 90% (27/30) of thyroid cancer or multinodular hyperplasia samples, compared with 90% (27/30) of adjacent normal thyroid tissue specimens. All samples were negative for EBER1 sequences, while HPV DNA was not detected in either nodular or normal thyroid tissue. Conclusions This study suggests that BKV and EBV “infection” is an early event, occurring within normal tissue. Our findings do not show a clear role for the viruses examined, instead they suggest an “endemicity” pattern rather than a causal effect.

scholarly journals Increased Expression of the Na+/I− Symporter in Cultured Human Thyroid Cells Exposed to Thyrotropin and in Graves’ Thyroid Tissue*

1997 ◽  
Vol 82 (10) ◽  
pp. 3331-3336 ◽  
Author(s):  
Tsukasa Saito ◽  
Toyoshi Endo ◽  
Akio Kawaguchi ◽  
Masato Ikeda ◽  
Minoru Nakazato ◽  
...  
Keyword(s):  
Thyroid Tissue ◽  
Human Thyroid ◽  
Thyroid Peroxidase ◽  
Graves Disease ◽  
Intracellular Camp ◽  
Normal Thyroid Tissue ◽  
Thyroid Cells ◽  
Normal Thyroid ◽  
Hormone Synthesis ◽  
Messenger Ribonucleic Acid

Abstract The Na+/I− symporter (NIS) is important in hormone synthesis in the thyroid gland. NIS activity, as reflected by I− uptake, was increased by TSH (1 mU/mL) or forskolin (10μ mol/L) in primary cultured human thyroid cells. Northern blot analysis revealed that incubation of these cells with TSH or forskolin for 24 h increased the abundance of NIS messenger ribonucleic acid (mRNA) 2.3- and 2.5-fold, respectively. Immunoblot analysis revealed 2.7- and 2.4-fold increases, respectively, in the amount of NIS protein after 48 h, suggesting that elevated levels of intracellular cAMP induced the expression of NIS in human thyrocytes. We then studied the levels of NIS mRNA and protein in Graves’ thyroid tissue and found that the amount of NIS mRNA in thyroid tissue from individuals with Graves’ disease (n = 5) was 3.8 times that in normal thyroid tissue (n = 5). The abundance of NIS mRNA was significantly correlated with that of thyroid peroxidase or thyroglobulin mRNAs, but not with that of TSH receptor mRNA, in the Graves’ and normal thyroid tissue specimens. The amount of NIS protein was also increased 3.1-fold in Graves’ thyroid tissue compared with that in normal thyroid tissue. The increased expression of NIS may thus contribute to the development of Graves’ disease.

scholarly journals MON-532 Characterization of the Angiogenic Factor SFRP2 in Papillary Thyroid Carcinoma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Wyatt O Wofford ◽  
Rupak Mukherjee ◽  
Julie Siegel ◽  
Denise Garcia ◽  
Eleanor Hilliard ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Thyroid Tissue ◽  
Angiogenic Factor ◽  
Papillary Thyroid ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid ◽  
Treatment Groups ◽  
Vehicle Treatment

Abstract Over the last decade, there has been an average annual increase of 3.1% in thyroid cancer diagnosis in the U.S. Papillary thyroid carcinoma (PTC) accounts for 80% of all thyroid cancer diagnoses. However, few molecular markers exist to identify clinically aggressive phenotypes. The angiogenic factor, secreted frizzled-related protein 2 (SFRP2), is associated with a poor prognosis in several malignancies including breast cancer and melanoma. The role of SFRP2 in PTC has yet to be investigated. The aims of this study were to determine the differential expression of SFRP2 in PTC, benign thyroid adenomas, normal thyroid tissue (from patients without cancer), and normal adjacent tissue (NAT) (non-cancerous tissue from patients with PTC) and investigate the role of SFRP2 in tumor development in two PTC cell lines, PTC classical variant (PTC-CV) and PTC follicular variant (PTC-FV), upon treatment with a humanized anti-SFRP2 monoclonal antibody (hSFRP2 mAb). Immunohistochemistry (IHC) was performed using human tissue protein microarrays including 226 PTC, 79 benign adenomas, 112 NAT, and 30 normal thyroid tissue samples. In-vitro proliferation and apoptosis experiments were performed on MDA-T41 (PTC-CV) and MDA-T68 (PTC-FV) cell lines by treating with hSFRP2 mAb, Xolair IgG control, and a vehicle control. SFRP2 expression was significantly higher in PTC compared with benign adenomas and normal thyroid (mean expression scores 9, 6, and 1, respectively; p<0.05). SFRP2 expression was significantly higher in NAT than normal thyroid (mean expression score 4 and 0, respectively, p<0.05). Apoptotic rates were increased by 40% and 62% in the PTC-CV hSFRP2 mAb treatment group compared with the Xolair and vehicle treatment groups, respectively (p<0.05). Apoptotic rates were increased by 126% and 59% in the PTC-FV hSFRP2 mAb treatment group compared with the Xolair and vehicle treatment groups, respectively (p<0.05). Treatment with hSFRP2 mAb had no significant effect on proliferation in either cell line. In conclusion, SFRP2 expression is significantly higher in PTC than in benign adenomas and normal thyroid tissue. SFRP2 expression in NAT is significantly higher than in normal thyroid tissue and not significantly different from benign adenomas. SFRP2 expression in nonmalignant tissue adjacent to PTC could be due to expression in the tumor microenvironment. Treatment with a novel hSFPR2 mAb increases apoptotic rates in two different PTC cell lines. These data suggest that SFPR2 is involved in tumorigenesis of PTC.

scholarly journals A comprehensive mass spectral library for human thyroid tissues

2021 ◽  
Author(s):  
Yaoting Sun ◽  
Lu Li ◽  
Weigang Ge ◽  
Zhen Dong ◽  
Wei Liu ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Thyroid Nodules ◽  
Thyroid Tissue ◽  
Follicular Adenoma ◽  
Human Thyroid ◽  
Papillary Thyroid ◽  
Spectral Library ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid

Thyroid nodules occur in about 60% of the population. Current diagnostic strategies, however, often fail at distinguishing malignant nodules before surgery, thus leading to unnecessary, invasive treatments. As proteins are involved in all physio/pathological processes, a proteome investigation of biopsied nodules may help correctly classify and identify malignant nodules and discover therapeutic targets. Quantitative mass spectrometry data-independent acquisition (DIA) enables highly reproducible and rapid throughput investigation of proteomes. An exhaustive spectral library of thyroid nodules is essential for DIA yet still unavailable. This study presents a comprehensive thyroid spectral library covering five types of thyroid tissue: multinodular goiter, follicular adenoma, follicular and papillary thyroid carcinoma, and normal thyroid tissue. Our library includes 925,330 transition groups, 157,548 peptide precursors, 121,960 peptides, 9941 protein groups, and 9826 proteins from proteotypic peptides. This library resource was evaluated using three papillary thyroid carcinoma samples and their corresponding adjacent normal thyroid tissue, leading to effective quantification of up to 7863 proteins from biopsy-level thyroid tissues.

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