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

Carlos Bais, Albert Van Geelen, Pilar Eroles, Agata Mutlu, Chiara Chiozzini, Sergio Dias, Roy L. Silverstein, Shahin Rafii, Enrique A. Mesri

Research output: Contribution to journalArticle

195 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)131-143
Number of pages13
JournalCancer Cell
Volume3
Issue number2
DOIs
StatePublished - Feb 2003

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ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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