Document Detail

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.
MedLine Citation:
PMID:  19499990     Owner:  NLM     Status:  MEDLINE    
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.
Matteo Landriscina; Annamaria Piscazzi; Annarita Fabiano; Francesca Maddalena; Eleonora Costantino; Anna Farese; Pantaleo Bufo; Mauro Cignarelli
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Thyroid : official journal of the American Thyroid Association     Volume:  19     ISSN:  1557-9077     ISO Abbreviation:  Thyroid     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-08     Completed Date:  2009-08-19     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9104317     Medline TA:  Thyroid     Country:  United States    
Other Details:
Languages:  eng     Pagination:  629-37     Citation Subset:  IM    
Department of Medical Sciences, University of Foggia, Foggia, Italy.
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MeSH Terms
Antineoplastic Agents / 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
Microscopy, Confocal
Neovascularization, Pathologic / pathology*
RNA, Neoplasm / biosynthesis,  genetics
Receptor, Epidermal Growth Factor / biosynthesis,  drug effects,  physiology*
S Phase / drug effects
Signal Transduction / drug effects*
Tetrazolium Salts
Thyroid Neoplasms / drug therapy*,  pathology*
Thyrotropin / physiology*
Reg. No./Substance:
0/Antineoplastic Agents; 0/RNA, Neoplasm; 0/Tetrazolium Salts; 0/Thiazoles; 298-93-1/thiazolyl blue; 9002-71-5/Thyrotropin; EC, Epidermal Growth Factor

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