Τίτλος:
Expression analysis of B-Raf oncogene in V600E-negative benign and malignant tumors of the thyroid gland: Correlation with late disease onset
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
B-Raf, a member of the Raf serine/threonine kinase family, is an intermediate molecule in the mitogen-activated protein kinase pathway, which relays extracellular signals from the cell membrane to the nucleus via a cascade of phosphorylation events, ultimately promoting cancer development. This pathway is usually activated in human neoplasias. The purpose of this study was to investigate the role of B-Raf in thyroid pathology. We scanned for the presence of mutations at codon 600 (V → E) of the B-Raf gene, using a PCR-RFLP assay. In tumors with no mutation (32 benign and malignant thyroid tumors) and in their adjacent normal tissue, we measured the expression levels of B-Raf gene, using a quantitative real-time PCR (qPCR) assay. B-Raf expression in V600E-negative tumors deviated from the normal pattern, since it was overexpressed in 42 % of benign samples and downregulated in 54 % of malignant specimens. Hashimoto's thyroiditis also seemed to play an important role, since benign specimens with Hashimoto's thyroiditis had a 2.2-fold higher B-Raf expression than samples without thyroiditis (1.71 ± 0.63 vs. 0.78 ± 0.13). Statistical analysis revealed that B-Raf deregulation postponed disease onset by more than 10 years in both benign and malignant thyroid (benign: 55.6 ± 3.9 vs. 45.3 ± 3.3, p = 0.049; malignant: 52.2 ± 3.5 vs. 33.0 ± 7.9, p = 0.020). From the above results, we deduce that in the absence of mutation activation, B-Raf overexpression or downregulation is a protective event, since it delays the development of both malignant and benign thyroid tumors. © 2012 Springer Science+Business Media New York.
Συγγραφείς:
Derdas, S.P.
Soulitzis, N.
Balis, V.
Sakorafas, G.H.
Spandidos, D.A.
Περιοδικό:
Medical Oncology
Λέξεις-κλειδιά:
B Raf kinase; B Raf kinase; BRAF protein, human; transcriptome, adult; article; clinical article; codon; disease course; down regulation; female; gene expression; gene mutation; Hashimoto disease; human; male; oncogene; polymerase chain reaction; priority journal; quantitative analysis; real time polymerase chain reaction; restriction fragment length polymorphism; thyroid cancer; cancer staging; genetics; Hashimoto disease; metabolism; middle aged; mutation; onset age; thyroid tumor, Age of Onset; Female; Hashimoto Disease; Humans; Male; Middle Aged; Mutation; Neoplasm Staging; Polymorphism, Restriction Fragment Length; Proto-Oncogene Proteins B-raf; Real-Time Polymerase Chain Reaction; Thyroid Neoplasms; Transcriptome
DOI:
10.1007/s12032-012-0336-3
