Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros

Banco de datos
Tipo del documento
Publication year range
1.
Oncogene ; 30(2): 190-200, 2011 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-20818438

RESUMEN

Kaposi Sarcoma (KS) are opportunistic tumors, associated with human herpes virus 8 (HHV8) infection. KS development is highly favored by immune-depression and remains the second most frequent tumor in acquired immune deficiency syndrome patients. Although it has been shown that experimental expression of the HHV8 G-protein-coupled receptor (vGPCR) in the endothelial compartment is alone sufficient to recapitulate the formation and progression of KS-like lesions, its functional effects on endothelial homeostasis are not fully understood. Here we show that vGPCR expression in endothelial cells induces an increase in paracellular permeability both in vivo and in vitro. By using pharmacological inhibitors and small interference RNA-based knockdown, we demonstrate an essential role for the PI(3)Kinase-γ/Rac nexus in vGPCR-mediated permeability. This was further accompanied by dramatic remodeling of VE-cadherin-dependent cell-cell junctions. Importantly, this in vitro vGPCR-initiated signaling signature was observed in a large panel of human KS. Altogether, our results support the hypothesis that endothelial vGPCR signaling is co-opted in KS, and unveil new key cellular targets for therapeutic intervention.


Asunto(s)
Antígenos CD/metabolismo , Cadherinas/metabolismo , Herpesvirus Humano 8 , Receptores de Quimiocina/metabolismo , Sarcoma de Kaposi/virología , Neoplasias Cutáneas/virología , Síndrome de Inmunodeficiencia Adquirida/metabolismo , Síndrome de Inmunodeficiencia Adquirida/virología , Androstadienos/farmacología , Animales , Permeabilidad Capilar/efectos de los fármacos , Línea Celular , Cromonas/farmacología , Cinamatos/farmacología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/virología , Inhibidores Enzimáticos/farmacología , Femenino , Furanos/farmacología , Humanos , Indoles/farmacología , Uniones Intercelulares/efectos de los fármacos , Uniones Intercelulares/metabolismo , Ratones , Ratones Desnudos , Morfolinas/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Piridinas/farmacología , Pirimidinas/farmacología , Quinoxalinas/farmacología , ARN Interferente Pequeño/genética , Sarcoma de Kaposi/tratamiento farmacológico , Sarcoma de Kaposi/patología , Piel/metabolismo , Piel/virología , Neoplasias Cutáneas/tratamiento farmacológico , Sulfonamidas/farmacología , Tiazolidinedionas/farmacología , Wortmanina
SELECCIÓN DE REFERENCIAS
Detalles de la búsqueda