Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR. Cancer Cell 2003 Feb;3(2):131-43
Date
03/07/2003Pubmed ID
12620408DOI
10.1016/s1535-6108(03)00024-2Scopus ID
2-s2.0-0142213135 (requires institutional sign-in at Scopus site) 212 CitationsAbstract
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.
Author List
Bais C, Van Geelen A, Eroles P, Mutlu A, Chiozzini C, Dias S, Silverstein RL, Rafii S, Mesri EAAuthor
Roy L. Silverstein MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ApoptosisCell Transformation, Neoplastic
Cells, Cultured
Endothelial Growth Factors
Endothelium, Vascular
Herpesvirus 8, Human
Humans
Intercellular Signaling Peptides and Proteins
Lymphokines
Phosphatidylinositol 3-Kinases
Phosphorylation
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
