The beta-catenin axis integrates multiple signals downstream from RET/papillary thyroid carcinoma leading to cell proliferation. (Articolo in rivista)

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Label
  • The beta-catenin axis integrates multiple signals downstream from RET/papillary thyroid carcinoma leading to cell proliferation. (Articolo in rivista) (literal)
Anno
  • 2009-01-01T00:00:00+01:00 (literal)
Alternative label
  • Castellone MD; De Falco V; Rao DM, Bellelli R; Muthu M; Basolo F; Fusco A; Gutkind JS; Santoro M. (2009)
    The beta-catenin axis integrates multiple signals downstream from RET/papillary thyroid carcinoma leading to cell proliferation.
    in Cancer research (Chic. Ill.)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Castellone MD; De Falco V; Rao DM, Bellelli R; Muthu M; Basolo F; Fusco A; Gutkind JS; Santoro M. (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Castellone MD, Istituto di Endocrinologia ed Oncologia Sperimentale ''G. Salvatore,'' Consiglio Nazionale delle Ricerche, c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare ''L. Califano,'' Universita Federico II, Naples, Italy; De Falco V, Dipartimento di Biologia e Patologia Cellulare e Molecolare ''L. Califano,'' Universita Federico II, Naples, Italy; Rao DM, Dipartimento di Biologia e Patologia Cellulare e Molecolare ''L. Califano,'' Universita Federico II, Naples, Italy;Department of Genetics, Institute of Basic Molecular Sciences, University of Madras, Madras, India; Bellelli R, Dipartimento di Biologia e Patologia Cellulare e Molecolare ''L. Califano,'' Universita Federico II, Naples, Italy; Muthu M, Dipartimento di Biologia e Patologia Cellulare e Molecolare ''L. Califano,'' Universita Federico II, Naples, Italy; Basolo F, Division of Pathology, Department of Surgery, University of Pisa, Pisa, Italy; Fusco A, Istituto di Endocrinologia ed Oncologia Sperimentale ''G. Salvatore,'' Consiglio Nazionale delle Ricerche, c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare ''L. Califano,'' Universita Federico II, Naples, Italy; Gutkinf JS, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland Santoro M, Istituto di Endocrinologia ed Oncologia Sperimentale ''G. Salvatore,'' Consiglio Nazionale delle Ricerche, c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare ''L. Califano,'' Universita Federico II, Naples, Italy; (literal)
Titolo
  • The beta-catenin axis integrates multiple signals downstream from RET/papillary thyroid carcinoma leading to cell proliferation. (literal)
Abstract
  • RET/papillary thyroid carcinoma (RET/PTC) oncoproteins result from the in-frame fusion of the RET receptor tyrosine kinase domain with protein dimerization motifs encoded by heterologous genes.Her e, we show that RET/PTC stimulates the B-catenin pathway.By stimulating PI3K/AKT and Ras/ extracellular signal-regulated kinase (ERK), RET/PTC promotes glycogen synthase kinase 3B (GSK3B) phosphorylation, thereby reducing GSK3B-mediated NH2-terminal B-catenin (Ser33/Ser37/Thr41) phosphorylation.In addition, RET/PTC physically interacts with B-catenin and increases its phosphotyrosine content.The increased free pool of S/T(nonphospho)/ Y(phospho)B-catenin is stabilized as a result of the reduced binding affinity for the Axin/GSK3B complex and activates the transcription factor T-cell factor/lymphoid enhancer factor. Moreover, through the ERK pathway, RET/PTC stimulates cyclic AMP-responsive element binding protein (CREB) phosphorylation and promotes the formation of a B-catenin- CREB-CREB-binding protein/p300 transcriptional complex. Transcriptional complexes containing B-catenin are recruited to the cyclin D1 promoter and a cyclin D1 gene promoter reporter is active in RET/PTC-expressing cells.Silencing of B-catenin by small interfering RNA inhibits proliferation of RET/PTC-transformed PC Cl3 thyrocytes, whereas a constitutively active form of B-catenin stimulates autonomous proliferation of thyroid cells.Thus, multiple signaling events downstream from RET/PTC converge on B-catenin to stimulate cell proliferation. (literal)
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