Τίτλος:
Epidermal growth factor receptor as a therapeutic target in human thyroid carcinoma: Mutational and functional analysis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Context: The epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase (TK) receptor that mediates proliferation and survival signaling, is expressed in a wide variety of normal and neoplastic tissues. EGFR inhibitors have produced objective responses in patients with non-small-cell lung carcinomas harboring activating EGFR TK domain somatic mutations. Objective and Methods: Because the EGFR pathway has been reported to be important for the pathophysiology of thyroid carcinoma, we investigated the expression and mutational status of EGFR in 14 thyroid carcinoma cell lines as well as its functional role by evaluating their in vitro sensitivity to AEE788, a new dual-family EGFR/ErbB2 and vascular endothelial growth factor receptor TK inhibitor. We also evaluated the mutational status, mRNA and protein expression, as well as phosphorylation status of EGFR in a panel of thyroid carcinoma specimens. Results: EGFR expression and phosphorylation in the thyroid carcinoma cell lines and tissue specimens were present but not stronger than in noncancerous thyroid tissue. EGFR TK domain mutations were detected in two of 62 histological specimens (3.2%) but not in cell lines. All thyroid carcinoma cell lines were significantly less sensitive (IC50 at least 25-fold higher) in vitro to AEE788 than a primary culture of EGFR-mutant lung carcinoma cells. Conclusions: Thyroid carcinoma cells overall are poorly responsive to clinically relevant concentrations of AEE788 in vitro. The presence of EGFR-activating TK domain mutations may identify a small minority of thyroid cancer patients that may benefit from EGFR inhibitors, but additional preclinical evidence of efficacy is needed. Copyright © 2006 by The Endocrine Society.
Συγγραφείς:
Mitsiades, C.S.
Kotoula, V.
Poulaki, V.
Sozopoulos, E.
Negri, J.
Charalambous, E.
Fanourakis, G.
Voutsinas, G.
Tseleni-Balafouta, S.
Mitsiades, N.
Περιοδικό:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
Εκδότης:
Japan Endocrine Society
Λέξεις-κλειδιά:
epidermal growth factor receptor; epidermal growth factor receptor 2; vasculotropin receptor, adolescent; adult; aged; article; female; functional assessment; human; human cell; in vitro study; major clinical study; male; mutational analysis; priority journal; protein expression; protein phosphorylation; thyroid carcinoma
DOI:
10.1210/jc.2006-0055
