title: A functional genomics approach to Kaposi's sarcoma.
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.
authors.affiliation: Vaccine and Gene Therapy Institute and Department of Molecular Microbiology and Immunology, Oregon Health Science University, Portland, Oregon 97239, USA.
authors.forename: Ashlee V
authors.initials: AV
authors.lastname: Moses
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jarvis
authors.forename: Camilo
authors.initials: C
authors.lastname: Raggo
authors.forename: Yolanda C
authors.initials: YC
authors.lastname: Bell
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ruhl
authors.forename: B G Mattias
authors.initials: BG
authors.lastname: Luukkonen
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Griffith
authors.forename: Cecily L
authors.initials: CL
authors.lastname: Wait
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Druker
authors.forename: Michael C
authors.initials: MC
authors.lastname: Heinrich
authors.forename: Jay A
authors.initials: JA
authors.lastname: Nelson
authors.forename: Klaus
authors.initials: K
authors.lastname: Fruh
mesh_terms: D001549:Benzamides; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics; D002472:Cell Transformation, Viral / Q000187:drug effects / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000821:virology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020869:Gene Expression Profiling; D023281:Genomics; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D000068877:Imatinib Mesylate; D020411:Oligonucleotide Array Sequence Analysis; D010879:Piperazines / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology; D016372:RNA, Antisense / Q000235:genetics / Q000494:pharmacology; D012514:Sarcoma, Kaposi / Q000209:etiology* / Q000235:genetics*; D014774:Virulence / Q000235:genetics
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; C000715470:MAS1 protein, human; D010879:Piperazines; D000090063:Proto-Oncogene Mas; D011743:Pyrimidines; D016372:RNA, Antisense; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit