| Targeting epidermal growth factor receptor 1 signaling in human thyroid-stimulating hormone-independent thyroid carcinoma FRO cells results in a more chemosensitive and less angiogenic phenotype. | |
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MedLine Citation:
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PMID: 19499990 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Poorly differentiated and anaplastic thyroid cancers are aggressive malignancies unresponsive to standard treatments. The mechanisms responsible for the progression of thyroid tumors toward a thyroid-stimulating hormone (TSH)-independent phenotype are still under discussion, and a better understanding of them may provide novel molecular targets for the treatment of this disease. We evaluated the hypothesis that epithelial growth factor (EGF) signaling may play a role in favoring the loss of TSH dependency in human differentiated thyroid tumor cells. METHODS: The sensitivity to EGF stimulation was evaluated in follicular thyroid carcinoma WRO cells that retain some features of thyroid cell differentiation and in undifferentiated TSH-independent thyroid carcinoma FRO cells. RESULTS: It was observed that, while both cell lines are characterized by a similar EGF-dependent activation of the RAS/MAPK signaling pathway, only FRO cells exhibited a significant induction of phosphoAKT, cell proliferation, and migration as well as the up-regulation of vascular endothelial growth factor-A expression in response to EGF. On the other hand, the inhibition of epidermal growth factor receptor 1 signaling by its tyrosine kinase inhibitor, erlotinib, caused a selective down-regulation of FRO cell proliferation and induced a phenotype more sensitive to the proapoptotic activity of anthracyclins and taxoids. By contrast, the protracted stimulation of TSH-dependent WRO cells with EGF induced the loss of TSH dependency and the rearrangement of F-actin cytoskeleton. CONCLUSIONS: These results suggest that the acquired sensitivity to EGF in these thyroid tumor cells may be responsible for the loss of differentiation in the transition toward a TSH-independent, invasive, and chemoresistant phenotype. |
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Authors:
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Matteo Landriscina; Annamaria Piscazzi; Annarita Fabiano; Francesca Maddalena; Eleonora Costantino; Anna Farese; Pantaleo Bufo; Mauro Cignarelli |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Thyroid : official journal of the American Thyroid Association Volume: 19 ISSN: 1557-9077 ISO Abbreviation: Thyroid Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-06-08 Completed Date: 2009-08-19 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9104317 Medline TA: Thyroid Country: United States |
Other Details:
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Languages: eng Pagination: 629-37 Citation Subset: IM |
Affiliation:
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Department of Medical Sciences, University of Foggia, Foggia, Italy. m.landriscina@unifg.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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therapeutic use* Blotting, Western Cell Differentiation / drug effects Cell Line, Tumor Cell Movement / drug effects Cell Survival / drug effects Down-Regulation / drug effects Drug Resistance, Neoplasm Humans Microscopy, Confocal Neovascularization, Pathologic / pathology* Phenotype RNA, Neoplasm / biosynthesis, genetics Receptor, Epidermal Growth Factor / biosynthesis, drug effects, physiology* S Phase / drug effects Signal Transduction / drug effects* Tetrazolium Salts Thiazoles Thyroid Neoplasms / drug therapy*, pathology* Thyrotropin / physiology* |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/RNA, Neoplasm; 0/Tetrazolium Salts; 0/Thiazoles; 298-93-1/thiazolyl blue; 9002-71-5/Thyrotropin; EC 2.7.10.1/Receptor, Epidermal Growth Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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