Document Detail

Interrelated overexpression of endothelial and inducible nitric oxide synthases, endothelin-1 and angiogenic factors in human papillary thyroid carcinoma.
MedLine Citation:
PMID:  16712675     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Nitric oxide (NO) and endothelin-1 (ET-1) are involved in carcinogenesis. Overexpression of the ET-1 axis has been demonstrated in papillary thyroid carcinoma (PTC). This study investigated the expression of NO synthases (NOS) and their relationship with expression of ET-1 and angiogenic markers in PTC. DESIGN AND PATIENTS: Expression of NOS, angiogenic markers [vascular endothelial growth factor (VEGF), angiopoietin-1 and angiopoietin-2] and their receptors was studied in surgical thyroid samples obtained from 22 patients aged 15-68 years. Three groups were constituted: normal thyroid (n = 5), Hashimoto's thyroiditis (n = 9) and PTC (n = 8). RESULTS: Immunohistochemistry disclosed NOS2 and NOS3 immunoreactivity in PTC cells, the percentage of positive cells being greater than normal (P < 0.02). Real-time quantitative polymerase chain reaction (RTQ-PCR) showed that NOS2 and NOS3 mRNA levels were, respectively, increased (P < 0.02) by 2.6 +/- 0.6 and 4.2 +/- 1.1 times in PTC. RTQ-PCR demonstrated that VEGF, its receptors VEGFR-1 and VEGFR-2, and angiopoietin-2 and its receptor (Tie2) were also overexpressed (P < 0.05) in PTC. Correlations were found between ET-1 expression and that of NOS2, angiopoietin-1 and -2 (P < 0.05). NOS2 mRNA levels also correlated with those of NOS3 and angiopoietin-2 (P < 0.05). In thyroiditis, NOS2 immunoreactivity was observed in inflammatory cells whereas NOS2 mRNA levels were 12.1 +/- 1.6 times higher than normal (P < 0.005). CONCLUSIONS: This study revealed an activation of the NO pathway in thyroid carcinoma, which is interrelated to the ET-1 axis, both systems being overexpressed in concert with angiogenic factors. This global system might play a role in carcinogenesis and constitutes a potential target for anticancer therapy.
Julian E Donckier; Luc Michel; Monique Delos; Xavier Havaux; Ronald Van Beneden
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Clinical endocrinology     Volume:  64     ISSN:  0300-0664     ISO Abbreviation:  Clin. Endocrinol. (Oxf)     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-22     Completed Date:  2006-09-15     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0346653     Medline TA:  Clin Endocrinol (Oxf)     Country:  England    
Other Details:
Languages:  eng     Pagination:  703-10     Citation Subset:  IM    
Department of Internal Medicine, Surgery and Pathology, University Hospital of Mont-Godinne, Université Catholique de Louvain, Yvoir, Belgium.
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MeSH Terms
Angiopoietin-1 / analysis,  genetics
Angiopoietin-2 / analysis,  genetics
Carcinoma, Papillary / chemistry*
Case-Control Studies
Endothelin-1 / analysis*
Hashimoto Disease / metabolism
Immunohistochemistry / methods
Middle Aged
Nitric Oxide Synthase / analysis*,  genetics
Nitric Oxide Synthase Type II / analysis,  genetics
Nitric Oxide Synthase Type III / analysis,  genetics
RNA, Messenger / analysis
Receptor, TIE-2 / analysis,  genetics
Thyroid Neoplasms / chemistry*
Vascular Endothelial Growth Factor A / analysis*,  genetics
Vascular Endothelial Growth Factor Receptor-1 / analysis,  genetics
Vascular Endothelial Growth Factor Receptor-2 / analysis,  genetics
Reg. No./Substance:
0/Angiopoietin-1; 0/Angiopoietin-2; 0/Endothelin-1; 0/RNA, Messenger; 0/Vascular Endothelial Growth Factor A; EC Oxide Synthase; EC Oxide Synthase Type II; EC Oxide Synthase Type III; EC, TIE-2; EC Endothelial Growth Factor Receptor-1; EC Endothelial Growth Factor Receptor-2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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