scholarly journals Expression of SMAD proteins, TGF-beta/activin signaling mediators, in human thyroid tissues

2010 ◽  
Vol 54 (4) ◽  
pp. 406-412 ◽  
Author(s):  
Sílvia E. Matsuo ◽  
Ana Paula Z. P. Fiore ◽  
Simone M. Siguematu ◽  
Kátia N. Ebina ◽  
Celso U. M. Friguglietti ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Malignant Tumors ◽  
Follicular Adenoma ◽  
Human Thyroid ◽  
Nuclear Staining ◽  
Thyroid Tumors ◽  
Thyroid Cells ◽  
Cytoplasmic Staining ◽  
Activin Signaling ◽  
Smad Proteins

OBJECTIVE: To investigate the expression of SMAD proteins in human thyroid tissues since the inactivation of TGF-β/activin signaling components is reported in several types of cancer. Phosphorylated SMAD 2 and SMAD3 (pSMAD2/3) associated with the SMAD4 induce the signal transduction generated by TGF-β and activin, while SMAD7 inhibits this intracellular signaling. Although TGF-β and activin exert antiproliferative roles in thyroid follicular cells, thyroid tumors express high levels of these proteins. MATERIALS AND METHODS: The protein expression of SMADs was evaluated in multinodular goiter, follicular adenoma, papillary and follicular carcinomas by immunohistochemistry. RESULTS: The expression of pSMAD2/3, SMAD4 and SMAD7 was observed in both benign and malignant thyroid tumors. Although pSMAD2/3, SMAD4 and SMAD7 exhibited high cytoplasmic staining in carcinomas, the nuclear staining of pSMAD2/3 was not different between benign and malignant lesions. CONCLUSIONS: The finding of SMADs expression in thyroid cells and the presence of pSMAD2/3 and SMAD4 proteins in the nucleus of tumor cells indicates propagation of TGF-β/activin signaling. However, the high expression of the inhibitory SMAD7, mostly in malignant tumors, could contribute to the attenuation of the SMADs antiproliferative signaling in thyroid carcinomas.

scholarly journals AMP-activated protein kinase signaling is upregulated in papillary thyroid cancer

2013 ◽  
Vol 169 (4) ◽  
pp. 521-528 ◽  
Author(s):  
Ana Paula Vidal ◽  
Bruno M Andrade ◽  
Fernanda Vaisman ◽  
Juliana Cazarin ◽  
Luis Felipe Ribeiro Pinto ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Energy Levels ◽  
Staining Intensity ◽  
University Hospital ◽  
Human Thyroid ◽  
Papillary Thyroid ◽  
Thyroid Cells ◽  
Cytoplasmic Staining ◽  
Thyroid Carcinomas ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) is activated by the depletion in cellular energy levels and allows adaptive changes in cell metabolism and cell survival. Recently, our group described that AMPK plays an important role in the regulation of iodide and glucose uptake in thyroid cells. However, AMPK signaling pathway in human thyroid carcinomas has not been investigated so far.ObjectiveTo evaluate the expression and activity of AMPK in papillary thyroid carcinomas.MethodsWe examined total and phosphorylated AMPK (tAMPK and pAMPK) and phosphorylated acetyl-CoA-carboxylase (pACC) expressions through imunohistochemistry, using a tissue microarray block composed of 73 papillary thyroid carcinomas (PAP CA) or microcarcinomas (PAP MCA) and six adenoma (AD) samples from patients followed at the Federal University Hospital. The expression levels were compared with the non-neoplastic tissues from the same patient. Two different pathologists analyzed the samples and attributed scores of staining intensity and the proportion of stained cells. A total index was obtained by multiplying the values of intensity and the proportion of stained cells (INTxPROP).ResultstAMPK, pAMPK, and pACC showed a predominant cytoplasmic staining in papillary carcinomas, adenomas, and non-neoplastic thyroid tissues. However, the intensity and the proportion of stained cells were higher in carcinomas, so that a significant increase was found in the INTxPROP score both in PAP CA and PAP MCA, when compared with their respective controls.ConclusionOur results show unequivocally that AMPK pathway is highly activated in papillary thyroid carcinomas; however, more studies are necessary to understand the pathophysiological significance of AMPK activation in thyroid carcinogenesis.

The regulation of FSHβ transcription by gonadal steroids: testosterone and estradiol modulation of the activin intracellular signaling pathway

2007 ◽  
Vol 293 (1) ◽  
pp. E277-E285 ◽  
Author(s):  
Laura L. Burger ◽  
Daniel J. Haisenleder ◽  
Gordon M. Wotton ◽  
Kevin W. Aylor ◽  
Alan C. Dalkin ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Fold Increase ◽  
Female Rats ◽  
Signaling System ◽  
Primary Transcript ◽  
Intracellular Signaling Pathway ◽  
Activin Signaling ◽  
Male And Female Rats ◽  
Smad2 Phosphorylation ◽  
Smad Proteins

Recent reports suggest that androgens increase FSHβ transcription directly via the androgen receptor and by modulating activin signaling. Estrogens may also regulate FSHβ transcription in part through the activin system. Activin signaling can be regulated extracellularly via activin, inhibin, or follistatin (FS) or intracellularly via the Smad proteins. We determined the effects of androgen and estrogen on FSHβ primary transcript (PT) concentrations in male and female rats, and we correlated those changes with pituitary: activin βB mRNA, FS mRNA, the mRNAs for Smads2, -3, -4, and -7, and the phosphorylation (p) status of Smad2 and -3 proteins. In males, testosterone (T) increased FSHβ PT two- to threefold between 3 and 24 h and was correlated with reduced FS mRNA, transient increases in Smad2, -4, and -7 mRNAs, and a six- to 10-fold increase in pSmad2, and activin βB mRNA was unchanged. In females, T also increased FSHβ PT twofold and pSmad2 threefold but had no effect on activin βB, FS, or the Smad mRNAs. Androgen also increased Smad2 phosphorylation in gonadotrope-derived αT3 cells. In contrast, estradiol had no effect on FSHβ PT but transiently increased activin βB mRNA and suppressed FS mRNA before increasing FS mRNA at 24 h and increased Smads2, -3, and -7 mRNAs and pSmad2 threefold. In conclusion, T acts on the pituitary to increase FSHβ PT in both sexes and modulates FS mRNA, Smad mRNAs, and/or Smad2 phosphorylation. These findings suggest that T regulates FSHβ transcription, in part, through modulation of various components of the activin-signaling system.

Integrins in thyroid tissue: upregulation of alpha2beta1 in anaplastic thyroid carcinoma

1998 ◽  
pp. 104-112 ◽  
Author(s):  
T Dahlman ◽  
L Grimelius ◽  
G Wallin ◽  
K Rubin ◽  
K Westermark
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastases ◽  
Malignant Tumors ◽  
Thyroid Tissue ◽  
Follicular Adenoma ◽  
Nodular Goiter ◽  
Human Thyroid ◽  
Integrin Beta1 ◽  
Node Metastases ◽  
E Cadherin

OBJECTIVE: To evaluate the integrin pattern in the normal thyroid gland and in different pathological disorders including malignant tumors, because the aggressiveness of several malignant tumors correlates with alterations in the expression of one or more integrins. DESIGN: We examined the expression of integrins and E-cadherin immunohistochemically in a large and well-defined sample of normal and pathological human thyroid tissue. METHODS: Cryosections of 58 thyroid tissue specimens from normal tissue, thyrotoxicosis, nodular goiter, oxyphilic adenoma, follicular adenoma, follicular carcinoma, papillary carcinoma and anaplastic carcinoma, and three lymph node metastases were investigated immunohistochemically using monoclonal antibodies specifically recognizing the integrin beta1-, beta4-, alpha1-, alpha2-, alpha3-, alpha5- and alpha6-subunits, or E-cadherin. RESULTS: All thyroid epithelial cells expressed integrin beta1- and alpha3-subunits. Immunostaining of the beta4-subunit and the alpha6-subunits was found only in tumors. The staining pattern in the three lymph node metastases from papillary carcinomas did not differ from that in their primaries. Anaplastic carcinomas demonstrated neoexpression of the integrin alpha2-subunit. E-cadherin was detected in all tissues except anaplastic carcinomas. CONCLUSIONS: Neoexpression of alpha6beta4 was seen in most malignant tumors, whereas alpha2 was exclusively found in anaplastic carcinomas. In the latter, a loss of E-cadherin expression was also seen. These changes in cell adhesion molecule expression strongly suggest an association with the acquisition of proliferative and invasive properties.

scholarly journals Thyroid Follicular Adenoma with Tracheal Stenosis

2021 ◽  
Vol 6 (4) ◽  
Author(s):  
Kusunoki T ◽  
Wada R
Keyword(s):  
Tracheal Stenosis ◽  
Malignant Tumors ◽  
Follicular Adenoma ◽  
Thyroid Tumor ◽  
Thyroid Tumors ◽  
Thyroid Lymphoma ◽  
Chronic Thyroiditis ◽  
Preoperative Ct ◽  
Malignant Lesions ◽  
Benign Thyroid

Some cases of thyroid malignant tumors and thyroid lymphoma were reported to have caused tracheal stenosis and choking. Benign thyroid tumors with dyspnea due to tracheal stenosis are very rare. We experienced a benign thyroid tumor that caused tracheal stenosis and dyspnea. In the preoperative CT, there was tracheal stenosis due to enlarged bilateral thyroid lobes and the width of the stenotic lumen was 7mm. Subtotal thyroidectomy improved the dyspnea. Postoperative histopathologic examination confirmed follicular adenoma without malignant lesions or chronic thyroiditis. On postoperative CT, the tracheal stenosis had improved and the lumen had increased to 15mm. The above findings would suggest that it should be keep in mind that even benign thyroid tumors with tracheal stenosis of less than 7mm in the lumen have the possibility of causing dyspnea.

scholarly journals EGF and TGF-1 Effects on Thyroid Function

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Gabriella Mincione ◽  
Maria Carmela Di Marcantonio ◽  
Chiara Tarantelli ◽  
Sonia D'Inzeo ◽  
Arianna Nicolussi ◽  
...  
Keyword(s):  
Growth Factors ◽  
Cell Lines ◽  
Cross Talk ◽  
Early Stage ◽  
Tumor Promoter ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Thyroid Tumors ◽  
Thyroid Cells ◽  
Rat Thyroid

Normal epithelial thyroid cells in culture are inhibited by TGF-1. Instead, transformed thyroid cell lines are frequently resistant to its growth inhibitory effect. Loss of TGF- responsiveness could be due to a reduced expression of TGF- receptors, as shown in transformed rat thyroid cell lines and in human thyroid tumors, or to alterations of other genes controlling TGF- signal transduction pathway. However, in thyroid neoplasia, a complex pattern of alterations occurring during transformation and progression has been identified. Functionally, TGF-1 acts as a tumor suppressor in the early stage of transformation or as a tumor promoter in advanced cancer. This peculiar pleiotropic behaviour of TGF- may result from cross-talk with signalling pathways mediated by other growth factors, among which EGF-like ligands play an important role. This paper reports evidences on TGF-1 and EGF systems in thyroid tumors and on the cross-talk between these growth factors in thyroid cancer.

Primary Tissue Cultures of Benign and Malignant Human Thyroid Tumors: Effect of TSH

1988 ◽  
Vol 99 (1) ◽  
pp. 10-15 ◽  
Author(s):  
L. Komlos ◽  
R. Shimberg ◽  
I. Halbrecht ◽  
Y. Zohar ◽  
M. Strauss ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Malignant Tumors ◽  
Suppressive Therapy ◽  
Human Thyroid ◽  
Benign Tumors ◽  
Thyroid Tumors ◽  
Tissue Cultures ◽  
Vitro Effect ◽  
Primary Tissue

Many thyroid carcinomas seem to be dependent upon the thyroid growth-promoting properties of the thyroid stimulating hormone (TSH). The purpose of the present investigation was to compare the in vitro effect of TSH on tissue cultures derived from malignant and benign thyroid tumors. The results indicate that TSH can affect the morphology and protein synthesis of primary tissue cultures derived from benign and malignant thyroid tumors differently. The addition of TSH to cultures derived from benign tumors resulted in a reorganization of follicle-like structures of the monolayer and in a reduction of protein synthesis. In contrast to this, monolayers derived from carcinomas of the thyroid were not able to reorganize and their protein synthesis was not inhibited in the presence of TSH. For a better understanding of TSH suppressive therapy, we suggest testing the influence of TSH on a large number of tissue cultures derived from benign and malignant tumors of the thyroid.

scholarly journals Immunohistochemical Expression of p16 in Melanocytic Lesions: An Updated Review and Meta-analysis

2018 ◽  
Vol 142 (7) ◽  
pp. 815-828 ◽  
Author(s):  
Stephen S. Koh ◽  
David S. Cassarino
Keyword(s):  
Malignant Tumors ◽  
Meta Analysis ◽  
Molecular Testing ◽  
Nuclear Staining ◽  
Cytoplasmic Staining ◽  
Essential Information ◽  
Melanocytic Lesions ◽  
P16 Immunohistochemistry ◽  
Pubmed Database ◽  
Wide Range

Context.— Making an accurate diagnosis for melanocytic lesions has always been challenging for pathologists, especially when dealing with difficult-to-diagnose cases. Misdiagnosis of melanoma and melanocytic lesions in general has tremendous medical-legal implications, often leading to unnecessary and excessive use of adjunctive tests. Although molecular testing is of much interest and there is great support for its development, currently, for most melanocytic lesions, immunohistochemical studies remain the most practical method for assistance in the routine diagnosis of melanocytic lesions for the average pathologist. Objectives.— To review the practical use of p16 immunohistochemistry for evaluating melanocytic lesions, particularly for differentiating benign from malignant tumors, and to perform a meta-analysis of primary studies evaluating p16 immunohistochemistry in melanocytic lesions. Data Sources.— A PubMed database search for literature reporting melanocytic lesions and p16 immunohistochemistry was performed. Essential information from each study (number of samples, antibody used, collection dates, overall p16 immunohistochemistry results, and general method of interpretation) was tabulated and analyzed. Examples of representative cases showing p16 immunostaining pattern are also illustrated. Conclusions.— Incorporation of p16 immunohistochemistry for the diagnosis of melanocytic lesions is of limited use, especially for the purpose of differentiating benign from malignant lesions. Evaluation of multiple studies reveals a wide range of results. However, there appears to be some value for the use of p16 in distinguishing nodal nevi from metastatic melanoma within nodes. The method of interpretation (nuclear versus cytoplasmic staining) also appears to give differing results, as studies considering only nuclear staining appeared to show more consistent results from study to study.

scholarly journals RAP1GAP inhibits cytoskeletal remodeling and motility in thyroid cancer cells

2012 ◽  
Vol 19 (4) ◽  
pp. 575-588 ◽  
Author(s):  
Xiaoyun Dong ◽  
Waixing Tang ◽  
Stephen Stopenski ◽  
Marcia S Brose ◽  
Christopher Korch ◽  
...  
Keyword(s):  
Protein Expression ◽  
Functional Significance ◽  
Anaplastic Thyroid Carcinoma ◽  
Human Thyroid ◽  
Thyroid Tumors ◽  
Papillary Thyroid ◽  
Thyroid Cells ◽  
Normal Thyroid ◽  
Cytoskeletal Remodeling ◽  
Carcinoma Cell Lines

The functional significance of decreased RAP1GAP protein expression in human tumors is unclear. To identify targets of RAP1GAP downregulation in the thyroid gland, RAP1 and RAP2 protein expression in human thyroid cells and in primary thyroid tumors were analyzed. RAP1GAP and RAP2 were co-expressed in normal thyroid follicular cells. Intriguingly, RAP1 was not detected in normal thyroid cells, although it was detected in papillary thyroid carcinomas, which also expressed RAP2. Both RAP proteins were detected at the membrane in papillary thyroid tumors, suggesting that they are activated when RAP1GAP is downregulated. To explore the functional significance of RAP1GAP depletion, RAP1GAP was transiently expressed at the lowest level that is sufficient to block endogenous RAP2 activity in papillary and anaplastic thyroid carcinoma cell lines. RAP1GAP impaired the ability of cells to spread and migrate on collagen. Although RAP1GAP had no effect on protein tyrosine phosphorylation in growing cells, RAP1GAP impaired phosphorylation of focal adhesion kinase and paxillin at sites phosphorylated by SRC in cells acutely plated on collagen. SRC activity was increased in suspended cells, where it was inhibited by RAP1GAP. Inhibition of SRC kinase activity impaired cell spreading and motility. These findings identify SRC as a target of RAP1GAP depletion and suggest that the downregulation of RAP1GAP in thyroid tumors enhances SRC-dependent signals that regulate cellular architecture and motility.

scholarly journals Modulation of ACE-2 mRNA by inflammatory cytokines in human thyroid cells: a pilot study

Endocrine ◽  
2021 ◽  
Author(s):  
Francesca Coperchini ◽  
Gianluca Ricci ◽  
Laura Croce ◽  
Marco Denegri ◽  
Rubina Ruggiero ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Combination Treatment ◽  
Primary Cultures ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Mrna Levels ◽  
Thyroid Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pro Inflammatory Cytokines

Abstract Introduction Angiotensin-converting-enzyme-2 (ACE-2) was demonstrated to be the receptor for cellular entry of SARS-CoV-2. ACE-2 mRNA was identified in several human tissues and recently also in thyroid cells in vitro. Purpose Aim of the present study was to investigate the effect of pro-inflammatory cytokines on the ACE-2 mRNA levels in human thyroid cells in primary cultures. Methods Primary thyroid cell cultures were treated with IFN-γ and TNF-α alone or in combination for 24 h. ACE-2 mRNA levels were measured by RT-PCR. As a control, the levels of IFN-γ inducible chemokine (CXCL10) were measured in the respective cell culture supernatants. Results The mean levels of ACE-2 mRNA increased after treatment with IFN-γ and TNF-α in all the thyroid cell preparations, while the combination treatment did not consistently synergically increase ACE-2-mRNA. At difference, CXCL10 was consistently increased by IFN-γ and synergically further increased by the combination treatment with IFN-γ + TNF-α, with respect to IFN-γ alone. Conclusions The results of the present study show that IFN-γ and, to a lesser extent TNF-α consistently increase ACE-2 mRNA levels in NHT primary cultures. More interestingly, the combined stimulation (proven to be effective according to the synergic effect registered for CXCL10) produces different responses in terms of ACE-2 mRNA modulation. These results would suggest that elevated levels of pro-inflammatory cytokines could facilitate the entering of the virus in cells by further increasing ACE-2 expression and/or account for the different degree of severity of SARS-COV-2 infection. This hypothesis deserves to be confirmed by further specific studies.

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