TGF-beta 1 modulation of IGF-I signaling pathway in rat thyroid epithelial cells |
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| Authors: | Mincione Gabriella Esposito Diana L Di Marcantonio Maria Carmela Piccirelli Alessandro Cama Alessandro Colletta Giulia |
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| Affiliation: | Dipartimento di Oncologia e Neuroscienze, Facoltà di Medicina e Chirurgia, Università G. D'Annunzio, Via dei Vestini, 31, Chieti, Italy. g.mincione@unich.it |
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| Abstract: | Transforming growth factor beta 1 (TGF-beta 1) and insulin-like growth factor I (IGF-I) have contrasting effects on cell cycle regulation in thyroid cells and TGF-beta 1 induces a dramatic decrease in IGF-I-induced cell proliferation. The aim of the present study was to investigate the molecular mechanism of cross-talk between TGF-beta 1 and IGF-I in FRTL-5 cells. TGF-beta 1 affected IGF-I-stimulated insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation and its association with Grb2 protein. Moreover, TGF-beta 1 decreased the IGF-I-induced tyrosine phosphorylation of the adaptor protein CrkII and its association with the IGF-I receptor. These results were accompanied by TGF-beta 1 inhibition of IGF-I-stimulated mitogen-activated protein kinase phosphorylation and activation. Conversely, TGF-beta 1 did not alter IGF-I-stimulated IRS-1-associated phosphatidylinositol 3-kinase activity, IGF-I-induced tyrosine phosphorylation of Shc, and its binding to Grb2. Taken together, these findings provide a molecular basis for the growth-inhibitory action of TGF-beta 1 on the IGF-I-induced mitogenic effect. |
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| Keywords: | Insulin-like growth factor I Transforming growth factor β 1 Insulin receptor substrate 1 CrkII Mitogen-activated protein kinase Thyroid cells |
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