A functional genomics approach to Kaposi's sarcoma

Ashlee V. Moses, Michael A. Jarvis, Camilo Raggo, Yolanda C. Bell, Rebecca Ruhl, B. G.Mattias Luukkonen, Diana J. Griffith, Cecily L. Wait, Brian J. Druker, Michael C. Heinrich, Jay A. Nelson, Klaus Früh

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Kaposi's sarcoma (KS) is the most frequent malignancy afflicting acquired immune-deficiency syndrome (AIDS) patients. Tumor lesions are characterized by spindle cells of vascular origin and vascularization. Kaposi's sarcoma-associated herpes virus (KSHV) is consistently found in all forms of KS. Infection of dermal microvascular endothelial cells (DMVEC) with KSHV recapitulates spindle cell formation in vitro. We studied this transformation process by DNA microarray analysis comparing the RNA expression profiles of KSHV-infected and mock-infected DMVEC. Genes involved in tumorigenesis, angiogenesis, host defense, cell growth and differentiation, transcription, and metabolism were observed to change significantly upon infection with KSHV. One of the most consistently KSHV-induced genes was the receptor tyrosine kinase and proto-oncogene c-Kit. Inhibition of c-Kit activity with the pharmacological inhibitor of c-Kit signaling STI571 reversed the KSHV-induced morphological transformation of DMVEC. Moreover, overexpression studies showed that c-Kit was sufficient to induce spindle cell formation (Moses et al. J. Virol. 76(16): 8383-8399). These data demonstrate that microarrays are useful for the identification of pharmacological targets essential for KS tumorigenesis.

Original languageEnglish (US)
Pages (from-to)180-191
Number of pages12
JournalAnnals of the New York Academy of Sciences
Volume975
DOIs
StatePublished - Jan 1 2002

Keywords

  • Antisense
  • Kaposi's sarcoma-associated herpesvirus
  • Microarray
  • c-kit

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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