Document Detail

Expression of the Ring Ligase PRAJA2 in Thyroid Cancer.
MedLine Citation:
PMID:  22948757     Owner:  NLM     Status:  Publisher    
Introduction:In thyroid cells, binding of TSH to its receptor increases cAMP levels, sustaining thyrocytes growth and hormone production. The main cAMP effector enzyme is protein kinase A (PKA). Praja2 is a widely expressed RING (Really Interesting New Gene) ligase, which degrades the regulatory subunits of PKA, thus controlling the strength and duration of PKA signaling in response to cAMP. Differentiated thyroid cancer expresses a functional TSH receptor, and its growth and progression are positively regulated by TSH and cAMP signaling.Aim:We aimed to analyze the expression of praja2 in a group of 36 papillary thyroid cancer (PTC), 14 benign nodules, and six anaplastic thyroid cancers (ATC).Methods:We measured praja2 mRNA levels by quantitative RT-PCR and praja2 expression by Western blot and immunohistochemistry. Possible association between praja2 mRNA and the presence of known mutations was evaluated.Results:We found a statistical significant increase of mRNA levels in PTC tissue samples, compared with benign nodules and ATC. In particular, mRNA levels were maximal in differentiated thyroid cancer (PTC), progressively decreasing in more aggressive tumors, ATC having the lowest amount of praja2 mRNA. Accordingly, higher levels of praja2 protein were detected in lysates from PTC, compared with ATC. By immunohistochemistry, in PTC sections we observed a marked increase of cytoplasmic praja2 signal, which significantly decreased in less differentiated thyroid tumors, completely disappearing in ATC. Studies in cultured cells stably expressing RET/PTC1 oncogene or mutant BRAF revealed a direct correlation between praja2 mRNA levels and malignant phenotype of transformed cells. Similar results were obtained using thyroid cancer tissues carrying the same mutations.Conclusions:praja2 is markedly overexpressed in differentiated thyroid cancer, and its levels inversely correlate with the malignant phenotype of the tumor. Thus, praja2 is a novel cancer-related gene whose expression is linked to the histotype and mutational status of the thyroid tumor.
Silvia Cantara; Francesco D'Angeli; Paolo Toti; Luca Lignitto; Maria Grazia Castagna; Serena Capuano; Bellur S Prabhakar; Antonio Feliciello; Furio Pacini
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-4
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  -     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Section of Endocrinology and Metabolism (S.Can., F.D., M.G.C., S.Cap., F.P.), Department of Internal Medicine, Endocrinology, and Metabolism and Biochemistry, and Department of Human Pathology and Oncology (P.T.), University of Siena, 53100 Siena, Italy; Department of Microbiology and Immunology (B.S.P.), College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60637; and Department of Biology and Molecular and Cellular Pathology (L.L., A.F.), "L. Califano," University Federico II, 80131 Naples, Italy.
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