Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi's sarcomagenesis and can promote the tumorigenic potential of viral latent genes Journal Article


Authors: Montaner, S.; Sodhi, A.; Molinolo, A.; Bugge, T. H.; Sawai, E. T.; He, Y.; Li, Y.; Ray, P. E.; Gutkind, J. S.
Article Title: Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi's sarcomagenesis and can promote the tumorigenic potential of viral latent genes
Abstract: The Kaposi's sarcoma herpesvirus (KSHV) has been identified as the etiologic agent of Kaposi's sarcoma (KS), but initial events leading to KS development remain unclear. Characterization of the KSHV genome reveals the presence of numerous potential oncogenes. To address their contribution to the initiation of the endothelial cell-derived KS tumor, we developed a novel transgenic mouse that enabled endothelial cell-specific infection in vivo using virus expressing candidate KSHV oncogenes. Here we show that transduction of one gene, vGPCR, was sufficient to induce angioproliferative tumors that strikingly resembled human KS. Endothelial cells expressing vGPCR were further able to promote tumor formation by cells expressing KSHV latent genes, suggestive of a cooperative role among viral genes in the promotion of Kaposi's sarcomagenesis.
Keywords: immunohistochemistry; signal transduction; oncoprotein; promoter region; genetics; proto-oncogene proteins; cancer growth; nonhuman; methodology; animal cell; mouse; animal; electron microscopy; metabolism; animals; mice; microscopy, electron; animal tissue; cells, cultured; infection; gene expression; neoplasm proteins; animal experiment; animal model; in vivo study; physiology; avian leukosis oncovirus; carcinogenesis; transgenic mouse; genetic transduction; virology; animalia; avian leukosis virus; mus musculus; mice, transgenic; transduction, genetic; cell transformation, neoplastic; oncogene; genetic engineering; cell culture; vascular endothelium; endothelium, vascular; cell transformation; tumor protein; herpesviridae; kaposi sarcoma; sarcoma, kaposi; ultrastructure; chemokine receptor; receptors, chemokine; human herpesvirus 8; herpesvirus 8, human; virus protein; viral proteins; endothelium injury; promoter regions (genetics); viral genetics; human; priority journal; article; men1 protein, human; orf74 protein, human herpesvirus 8
Journal Title: Cancer Cell
Volume: 3
Issue: 1
ISSN: 1535-6108
Publisher: Cell Press  
Date Published: 2003-01-01
Start Page: 23
End Page: 36
Language: English
DOI: 10.1016/s1535-6108(02)00237-4
PUBMED: 12559173
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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  1. Yi Li
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