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

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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.

Original languageEnglish
Pages (from-to)131-143
Number of pages13
JournalCancer Cell
Volume3
Issue number2
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

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Human Herpesvirus 8
Vascular Endothelial Growth Factor Receptor-2
Kaposi's Sarcoma
G-Protein-Coupled Receptors
Vascular Endothelial Growth Factor A
Endothelial Cells
Autocrine Communication
Telomere Homeostasis
Herpesviridae
Human Umbilical Vein Endothelial Cells
Retroviridae
Phosphatidylinositol 3-Kinases
Oncogenes
Genes
Intercellular Signaling Peptides and Proteins
Phenotype
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR. / Bais, Carlos; Van Geelen, Albert; Eroles, Pilar; Mutlu, Agata; Chiozzini, Chiara; Dias, Sergio; Silverstein, Roy L.; Rafii, Shahin; Mesri, Enrique A.

In: Cancer Cell, Vol. 3, No. 2, 01.02.2003, p. 131-143.

Research output: Contribution to journalArticle

Bais, Carlos ; Van Geelen, Albert ; Eroles, Pilar ; Mutlu, Agata ; Chiozzini, Chiara ; Dias, Sergio ; Silverstein, Roy L. ; Rafii, Shahin ; Mesri, Enrique A. / Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR. In: Cancer Cell. 2003 ; Vol. 3, No. 2. pp. 131-143.
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AU - Chiozzini, Chiara

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