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Abstract:

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.

Registro:

Documento: Artículo
Título:Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR
Autor:Bais, C.; Van Geelen, A.; Eroles, P.; Mutlu, A.; Chiozzini, C.; Dias, S.; Silverstein, R.L.; Rafii, S.; Mesri, E.A.
Filiación:Laboratory of Viral Oncogenesis, Department of Medicine, Weill Med. Coll. of Cornell Univ., 1300 York Avenue, New York, NY 10021, United States
Division of Hematology-Oncology, Department of Medicine, Weill Med. Coll. of Cornell Univ., 1300 York Avenue, New York, NY 10021, United States
Department of Biology, Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Laboratorio di Virologia, Istituto Superiore di Sanita, Rome, Italy
Howard Hughes Medical Institute, Columbia University, College of Physicians and Surgeons, New York, NY 10032, United States
Center for Comparative Medicine, University of California, Davis, CA 95616, United States
Palabras clave: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
Año:2003
Volumen:3
Número:2
Página de inicio:131
Página de fin:143
DOI: http://dx.doi.org/10.1016/S1535-6108(03)00024-2
Título revista:Cancer Cell
Título revista abreviado:Cancer Cell
ISSN:15356108
CODEN:CCAEC
CAS:endothelial cell growth factor, 92880-73-4; phosphatidylinositol 3 kinase, 115926-52-8; protein kinase B, 148640-14-6; vasculotropin A, 489395-96-2; vasculotropin, 127464-60-2; 1-Phosphatidylinositol 3-Kinase, EC 2.7.1.137; AKT1 protein, human, EC 2.7.1.37; Endothelial Growth Factors; G protein-coupled receptor, Human herpesvirus 8; Intercellular Signaling Peptides and Proteins; Lymphokines; Protein-Serine-Threonine Kinases, EC 2.7.1.37; Proto-Oncogene Proteins c-akt, EC 2.7.1.37; Proto-Oncogene Proteins; Receptors, Chemokine; Telomerase, EC 2.7.7.49; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2, EC 2.7.1.112; Vascular Endothelial Growth Factors; Viral Proteins
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Citas:

---------- APA ----------
Bais, C., Van Geelen, A., Eroles, P., Mutlu, A., Chiozzini, C., Dias, S., Silverstein, R.L.,..., Mesri, E.A. (2003) . Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR. Cancer Cell, 3(2), 131-143.
http://dx.doi.org/10.1016/S1535-6108(03)00024-2
---------- CHICAGO ----------
Bais, C., Van Geelen, A., Eroles, P., Mutlu, A., Chiozzini, C., Dias, S., et al. "Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR" . Cancer Cell 3, no. 2 (2003) : 131-143.
http://dx.doi.org/10.1016/S1535-6108(03)00024-2
---------- MLA ----------
Bais, C., Van Geelen, A., Eroles, P., Mutlu, A., Chiozzini, C., Dias, S., et al. "Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR" . Cancer Cell, vol. 3, no. 2, 2003, pp. 131-143.
http://dx.doi.org/10.1016/S1535-6108(03)00024-2
---------- VANCOUVER ----------
Bais, C., Van Geelen, A., Eroles, P., Mutlu, A., Chiozzini, C., Dias, S., et al. Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR. Cancer Cell. 2003;3(2):131-143.
http://dx.doi.org/10.1016/S1535-6108(03)00024-2