Novel cellular genes essential for transformation of endothelial cells by Kaposi's sarcoma-associated herpesvirus

Camilo Raggo, Rebecca Ruhl, Shane McAllister, Henry Koon, Bruce J. Dezube, Klaus Frueh, Ashlee Moses

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is involved in the development of lymphoproliferative diseases and Kaposi's sarcoma. The oncogenicity of this virus is reflected in vitro by its ability to transform B cells and endothelial cells. Infection of dermal microvascular endothelial cells (DMVEC) transforms the cells from a cobblestone-like monolayer to foci-forming spindle cells. This transformation is accompanied by dramatic changes in the cellular transcriptome. Known oncogenes, such as c-Kit, are among the KSHV-induced host genes. We previously showed that c-Kit is an essential cellular component of the KSHV-mediated transformation of DMVEC. Here, we test the hypothesis that the transformation process can be used to discover novel oncogenes. When expression of a panel of KSHV-induced cellular transcripts was inhibited with antisense oligomers, we observed inhibition of DMVEC proliferation and foci formation using antisense molecules to RDC1 and Neuritin. We further showed that transformation of KSHV-infected DMVEC was inhibited by small interfering RNA directed at RDC1 or Neuritin. Ectopic expression of Neuritin in NIH 3T3 cells resulted in changes in cell morphology and anchorage-independent growth, whereas RDC1 ectopic expression significantly increased cell proliferation. In addition, both RDC1- and Neuritin-expressing cells formed tumors in nude mice. RDC1 is an orphan G protein-coupled receptor, whereas Neuritin is a growth-promoting protein known to mediate neurite outgrowth. Neither gene has been previously implicated in tumorigenesis. Our data suggest that KSHV-mediated transformation involves exploitation of the hitherto unrealized oncogenic properties of RDC1 and Neuritin.

Original languageEnglish (US)
Pages (from-to)5084-5095
Number of pages12
JournalCancer Research
Volume65
Issue number12
DOIs
StatePublished - Jun 15 2005

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Human Herpesvirus 8
Essential Genes
Endothelial Cells
Skin
Oncogenes
Cell Proliferation
NIH 3T3 Cells
Kaposi's Sarcoma
Growth
G-Protein-Coupled Receptors
Transcriptome
Nude Mice
Small Interfering RNA
Genes
Carcinogenesis
B-Lymphocytes
Viruses
Infection
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Novel cellular genes essential for transformation of endothelial cells by Kaposi's sarcoma-associated herpesvirus. / Raggo, Camilo; Ruhl, Rebecca; McAllister, Shane; Koon, Henry; Dezube, Bruce J.; Frueh, Klaus; Moses, Ashlee.

In: Cancer Research, Vol. 65, No. 12, 15.06.2005, p. 5084-5095.

Research output: Contribution to journalArticle

Raggo, Camilo ; Ruhl, Rebecca ; McAllister, Shane ; Koon, Henry ; Dezube, Bruce J. ; Frueh, Klaus ; Moses, Ashlee. / Novel cellular genes essential for transformation of endothelial cells by Kaposi's sarcoma-associated herpesvirus. In: Cancer Research. 2005 ; Vol. 65, No. 12. pp. 5084-5095.
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