scholarly journals DKK3 is a potential tumor suppressor gene in papillary thyroid carcinoma

2013 ◽  
Vol 20 (4) ◽  
pp. 507-514 ◽  
Author(s):  
De-tao Yin ◽  
Wenxun Wu ◽  
Mingchuang Li ◽  
Qi-en Wang ◽  
Hongqiang Li ◽  
...  

The expression of the Dickkopf homolog 3 (DKK3) gene is downregulated in some human cancers, suggesting a possible tumor suppressor role of this gene. The role and regulation ofDKK3in thyroid cancer have not been examined. In this study, we explored the relationship of promoter methylation with the inactivation ofDKK3and tumor behaviors in papillary thyroid carcinoma (PTC). We used methylation-specific PCR and RT-PCR to examine the promoter methylation and expression ofDKK3and tumor characteristics. We found mRNA expression ofDKK3in 44.9% of the PTC tissue samples vs 100% of the matched normal thyroid tissue samples (P<0.01). In contrast, an opposite distribution pattern ofDKK3gene methylation was observed; specifically, 38.8% of the PTC tissue samples vs 0% of the matched normal thyroid tissue samples harboredDKK3methylation. An inverse correlation between the promoter methylation and mRNA expression ofDKK3in PTC tissue samples was also observed. Moreover, we also found an inverse correlation betweenDKK3expression and some aggressive pathological characteristics of PTC, including high TNM stages and lymph node metastasis, but a positive correlation betweenDKK3promoter hypermethylation and pathological aggressiveness of the tumor. Treatment of the PTC cell line TPC-1 with the demethylating agent 5-azaC reducedDKK3promoter methylation and enhanced its expression, establishing functionally the impact ofDKK3methylation on its expression. Our data thus for the first time demonstrate that theDKK3gene is a potential tumor suppressor gene in thyroid cancer and that aberrant promoter methylation is an important mechanism for its downregulation, which may play a role in the tumorigenesis and aggressiveness of PTC.

2016 ◽  
Vol 70 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Matthias Pohl ◽  
Florian Grabellus ◽  
Karl Worm ◽  
Georg Arnold ◽  
Martin Walz ◽  
...  

AimsMany studies have previously reported a higher prevalence of papillary thyroid carcinomas (PTC) in patients with Graves' disease (GD). MicroRNAs (miRNAs) are small, non-coding RNAs that are upregulated in PTC compared with benign thyroid tissue. The objective of the study was to examine the miRNA expression of selected miRNAs that are known to be upregulated in PTC in patients with GD.MethodsParaffin embedded thyroid tissue from 159 patients with GD was screened for expression of the miRNAs 146b, 181b, 21, 221 and 222 by RT-PCR. The expression profiles of four normal thyroids, 50 PTCs without concomitant GD and 11 patients with untreated GD served as the controls.ResultsThe expression pattern of these miRNAs in patients with GD is intermediate between that of benign thyroid tissue (p<0.001) and PTC (in three out of five miRNAs, p<0.001). This corresponds to a 15-fold change for GD versus PTC, and a 31-fold change for GD versus normal thyroid tissue. The miRNA expression in 11 papillary microcarcinomas found in our study (a prevalence of 0.07) was not different from that in PTC samples from patients without GD for four of five miRNA types. Furthermore, we found a significant difference in the expression of miRNA 221/222 between treated and untreated GD tissue.ConclusionsIn conclusion, we found an intermediate expression of specific miRNAs in thyroid tissue from patients with GD that fell between the expression levels found in normal thyroid glands and PTC, which suggests a possible influence of certain miRNAs on developing PTC in patients with GD.


2003 ◽  
Vol 11 (3) ◽  
pp. 171-172
Author(s):  
Ivan Paunovic

The present data of growth factors, oncogenes, tumor-suppressor-genes and environmental factors can be summarized in thus: thyrotropin, growth factors and other hormones do increase thyrocyte growth and specific mutations of growth factor receptors (thyrotropin receptor [TSH-R], alpha subunit of hetero-trimeric transducer protein [GSP]) cause autonomously functioning thyroid tissue and differentiated thyroid carcinoma. In the thyroid, as in other organs, genes that are found to be differentially expressed between normal thyroid tissue and thyroid carcinomas can be used as targets for molecular-based diagnosis and therapy. Deregulation of tumor suppressor gene p53, however, parallels dedifferentiation of papillary and follicular thyroid cancer but has been found in few cases only. Iodide inhibiting thyrocyte growth will have to be investigated more intensively after sodium-iodide-symporter (NIS) has been cloned, and studies may now be available that could lead to form of conservative treatment in especially dedifferentiated thyroid cancer.


2006 ◽  
Vol 45 (8) ◽  
pp. 613-626 ◽  
Author(s):  
Lewis M. Brown ◽  
Steve M. Helmke ◽  
Stephen W. Hunsucker ◽  
Romana T. Netea-Maier ◽  
Simon A. Chiang ◽  
...  

2001 ◽  
Vol 47 (3) ◽  
pp. 6-10 ◽  
Author(s):  
I. I. Dedov ◽  
Ye. A. Troshina ◽  
N. V. Mazurina ◽  
A. Belfiore

Clinical implication of Met-hepatocytic growth factor receptor (Met/HGF-R) in thyroid adenocarcinoma tissue was studied on 163 operative thyroid samples (129papillary cancers, 21 follicular cancers, and 13 anaplastic cancers). 49 adenomas, 50 nodular goiters and 50 normal thyroids were compared. Expression of Met/HGF-R was estimated using semiquantitative immunohistochemical method including proportion (limits 0-5) and intensity (limits 0-5) of cell staining and calculation of Met/HGF-R total expression (limit 0-10). Met/HGF-R was not found in normal thyroid tissue, was absent or focally expressed in follicular and aplastic tumors, and was present in different amounts in papillary adenocarcinomas. It is suggested that low expression of Met/HGF-R is an indicator of unfavorable prognosis in papillary thyroid cancer.


Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1109 ◽  
Author(s):  
Chen-Kai Chou ◽  
Shun-Yu Chi ◽  
Fong-Fu Chou ◽  
Shun-Chen Huang ◽  
Jia-He Wang ◽  
...  

Male gender is a risk factor for mortality in patients with papillary thyroid carcinoma (PTC). This study investigated the impact of androgen receptor (AR) gene expression on the clinical features and progression of PTC. The levels of AR mRNA and protein in frozen, formalin-fixed, paraffin-embedded tissue samples from PTC and adjacent normal thyroid tissue were assessed by quantitative real-time polymerase chain reaction and immunohistochemical staining, respectively, and the relationships between AR expression and clinical features were analyzed. The thyroid cancer cell lines, BCPAP and TPC-1, were used to evaluate the effects of AR on the regulation of cell migration, and key epithelial–mesenchymal transition (EMT) markers. AR mRNA expression was significantly higher in normal thyroid tissue from men than women. The sex difference in AR mRNA expression diminished during PTC tumorigenesis, as AR mRNA expression levels were lower in PTC than normal thyroid tissues from both men and women. AR mRNA expression was significantly decreased in PTC patients with higher risk and in those with extrathyroidal extension. Overexpression of AR in BCPAP cells decreased cell migration and repressed the EMT process by down-regulating mRNA expression of N-cadherin, Snail1, Snail2, Vimentin, and TWIST1 and up-regulating E-cadherin gene expression. These results suggest that suppression of the androgen–AR axis may lead to aggressive tumor behavior in patients with PTC.


2001 ◽  
pp. 591-597 ◽  
Author(s):  
D Russo ◽  
S Bulotta ◽  
R Bruno ◽  
F Arturi ◽  
P Giannasio ◽  
...  

OBJECTIVE: The expression of two iodide transporters, the sodium/iodide symporter (NIS) and pendrin, was analyzed in thyroid tissues of patients with toxic multinodular goiter (TMNG) and non-toxic multinodular goiter (MNG). METHODS: The levels of NIS and pendrin proteins were analyzed in total protein extracts from nodular and non-nodular tissues by Western blot. RESULTS: In tissue samples from TMNG, we found an increased expression of NIS (2.5-fold) in the hot nodules, and similar levels between cold nodules and non-nodular tissues. In contrast, the levels of pendrin were slightly increased in both hot and cold nodules from TMNG, and decreased (about twofold) in cold nodules from MNG. We also noticed that there was no relationship between NIS and pendrin expression. CONCLUSIONS: Our data demonstrate that hot nodules from TMNG express a higher number of iodide transporters (mainly NIS), whereas cold nodules from TMNG, but not from MNG, show levels of the two proteins comparable with normal tissue, suggesting a role in vivo of TSH in maintaining the expression of NIS and pendrin protein in normal thyroid tissue. Finally, different mechanisms are involved in the regulation of NIS and pendrin expression.


Author(s):  
Vladimir Zaichick

Background: Thyroid benign nodules (TBNs) are the most common diseases of this endocrine gland and are common worldwide. Among TBNs the colloid goiter (CG) and thyroid adenoma (TA) are very frequentdiseases. Evaluation of variant of TBNs is clinically important for subsequent therapeutic interventions, as well as for a clearer understanding the etiology of these disorders. The aim of this exploratory study was to examine differences in the content offifty trace elements (TE) in CG and TA tissues. Methods: Thyroid tissue levels of TE have prospectively evaluated in 46 patients with CG and 19 patients with TA. Measurements have performed using a combination of non-destructive and destructive methods: instrumental neutron activation analysis with high resolution spectrometry of long-lived radionuclides (INAA-LLR) and inductively coupled plasma mass spectrometry (ICPMS), respectively. Tissue samples were divided into two portions. One was used for morphological study while the other was intended for TE analysis. Results: It was observed that in both CG and TA tissues the contents of Ag, Al, Cr, Hg, Mn, Th, and Zn increased, whereas the levels of Au, Be, Cs, Pb, Rb, Sb, Sc, Th, Yb, and Zr were unchanged in comparison with normal thyroid tissue. No differences were found between the TE contents of CG and TA. Conclusions: From results obtained, it was possible to conclude that the common characteristics of CG and TA tissue samples were of a high level of Ag, Al, Cr, Hg, Mn, Th, and Zn in comparison with normal thyroid and, therefore, these TE could be involved in etiology and pathogenesis of thyroid disorders such as CG and TA.                    Peer Review History: Received: 12 November 2021; Revised: 15 December; Accepted: 31 December, Available online: 15 January 2022 Academic Editor: Ahmad Najib, Universitas Muslim Indonesia,  Indonesia, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency.  Received file:                Reviewer's Comments: Average Peer review marks at initial stage: 6.5/10 Average Peer review marks at publication stage: 7.5/10 Reviewers: Prof. Dr. Hassan A.H. Al-Shamahy, Sana'a University, Yemen, [email protected] Rima Benatoui, Laboratory of Applied Neuroendocrinology, Department of Biology, Faculty of Science, Badji Mokhtar University Annaba, BP12 E L Hadjar–Algeria, [email protected] Similar Articles: COMPARISON OF LEVELS OF TWENTY CHEMICAL ELEMENTS IN NORMAL THYROID TISSUE AND HYPERTROPHIC THYROID TISSUE


Sign in / Sign up

Export Citation Format

Share Document