Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR

• Autores: Bais, C.; Van Geelen, A.; Eroles, P.; Mutlu, A.; Chiozzini, C.; Dias, S.; Silverstein, R.L.; Rafii, S.; Mesri, E.A.
• Año de publicación: 2003
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Cancer Cell 2003;3(2):131-143
• Materia: G protein coupled receptor; vasculotropin receptor 2; virus protein; AKT1 protein, human; chemokine receptor; endothelial cell growth factor; G protein coupled receptor, Human herpesvirus 8; G protein-coupled receptor, Human herpesvirus 8; lymphokine; oncoprotein; phosphatidylinositol 3 kinase; protein kinase B; protein serine threonine kinase; signal peptide; telomerase; vasculotropin; vasculotropin A; apoptosis; article; association; autocrine effect; cell immortalization; endothelium cell; human; human cell; Human herpesvirus 8; priority journal; protein expression; protein function; signal transduction; telomere; umbilical vein; cell culture; cell transformation; genetics; Kaposi sarcoma; metabolism; pathogenicity; pathology; phosphorylation; physiology; Retrovirus; vascular endothelium; virology; Herpesviridae; Human herpesvirus 8; Oncovirinae; Papovaviridae; 1-Phosphatidylinositol 3-Kinase; Apoptosis; Cell Transformation, Neoplastic; Cells, Cultured; Endothelial Growth Factors; Endothelium, Vascular; Herpesvirus 8, Human; Humans; Intercellular Signaling Peptides and Proteins; Lymphokines; Phosphorylation; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Receptors, Chemokine; Retroviridae; Sarcoma, Kaposi; Signal Transduction; Telomerase; Telomere; Umbilical Veins; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factors; Viral Proteins
• Institución: Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales

The G protein-coupled receptor oncogene (vGPCR) of the Kaposi's sarcoma (KS) associated herpesvirus (KSHV), an oncovirus implicated in angioproliferative neoplasms, induces angiogenesis by VEGF secretion. Accordingly, we found that expression of vGPCR in human umbilical vein endothelial cells (HUVEC) leads to immortalization with constitutive VEGF receptor-2/ KDR expression and activation. vGPCR immortalization was associated with anti-senescence mediated by alternative lengthening of telomeres and an anti-apoptotic response mediated by vGPCR constitutive signaling and KDR autocrine signaling leading to activation of the PI3K/AKT pathway. In the presence of the KS growth factor VEGF, this mechanism can sustain suppression of signaling by the immortalizing gene. We conclude that vGPCR can cause an oncogenic immortalizing event and recapitulate aspects of the KS angiogenic phenotype in human endothelial cells, pointing to this gene as a pathogenic determinant of KSHV.
Fil:Bais, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Mesri, E.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.