Browsing by Subject "Rho"

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    HGF/C-MET system pathways in benign and malignant histotypes of thyroid nodules: an immunohistochemical characterization
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Ruggeri, Rosaria Maddalena; Vitarelli, Enrica; Barresi, Gaetano; Trimarchi, Francesco; Benvenga, S.; Trovato, Maria
    Objective. Upon binding with HGF, the thyrosine-kinase receptor c-met induces cell growth, scattering and morphogenic effects via the trasducers STAT3 and phosphorylated-STAT3, PI3K/Akt, Rho. HGF, c-met and STAT3 are expressed with very high frequency in papillary thyroid carcinomas (PTC), suggesting a role in PTC. Herein we first investigate the simultaneous expression of HGF, c-met, STAT3, phosphor-STAT3, PI3K, Akt and Rho in thyroid nodules. Design and methods. Using immunohistochemistry, we studied: 30 colloid nodules (CN), 18 hyperplastic nodules (HN), 20 follicular adenomas (FA), 15 oncocytic adenomas (OA), 20 PTC, 16 follicular carcinomas (FTC) and 6 anaplastic carcinomas (ATC). Results. All 7 proteins were expressed in 15% of FA (with HGF, PI3K and Rho stromal reactivity) and 25% of PTC, and the combination HGF/c-met/STAT3/ pSTAT3/PI3K was expressed by all PTC, each protein being expressed by tumor cells. In contrast, 13/16 FTC (81%) exhibited immunoreactivity for PI3K (both epithelial and stromal), and 100% of ATC was PI3K+ (both epithelial and stromal) and Rho+ (epithelial). Epithelial expression of PI3K correlated with the clinical behavior of histotypes and, within FTC, the proportion of PI3K+ cells correlated with both the clinical and pathological stage (r=0.95; p<0.001). As for the shared epithelial expression of PI3K, this concerned approximately one-fourth of tumor cells in FTC and ATC vs one-thirtieth in PTC. Conclusions. Our data may have practical implications for the targeted medical therapy of thyroid cancer arising from the follicular epithelium
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    The Rho small GTPase Functions in health and disease
    (Murcia : F. Hernández, 2002) Toksoz, D.; Merdek, K.D.
    Cell shape changes, contractility, adhesion, migration, gene transcription, cytokinesis, membrane trafficking, and growth, require Rho small GTPase function. The basis for this is that Rho regulates actin filament assembly, and serum response factor (SRF)- mediated gene transcription. Upon activation by serum or cell adhesion, Rho stimulates a distinct signal transduction pathway that induces cytoskeletal and transcriptional responses through diverse effectors. Rho activity is tightly controlled by guanine nucleotide exchange factors, GTPase activating proteins, and guanine dissociation inhibitors. Dysregulation of the Rho pathway is implicated in multiple pathological conditions including cancer and metastasis, cardiovascular disease, bacterial and viral pathogenesis, hepatic disease, and developmental disorders.