 | MICROARRAYS, IMMUNE RESPONSES, AND VACCINES
Copyright © 2002 by the New York Academy of Sciences
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Annals of the New York Academy of Sciences 975:180-191 (2002)
© 2002 New York Academy of Sciences
A Functional Genomics Approach to Kaposi's Sarcoma
ASHLEE V. MOSESa,
MICHAEL A. JARVISa,
CAMILO RAGGOa,
YOLANDA C. BELLb,
REBECCA RUHLa,
B.G. MATTIAS LUUKKONENb,
DIANA J. GRIFFITHc,
CECILY L. WAITc,
BRIAN J. DRUKERc,
MICHAEL C. HEINRICHc,
JAY A. NELSONa AND
KLAUS FRÜHa
aVaccine and Gene Therapy Institute and Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon 97239, USA
bR.W. Johnson Pharmaceutical Research Institute, 3210 Merryfield Row, San Diego California 92121, USA
cDivision of Hematology and Medical Oncology, Oregon Health & Science University and Portland Veterans Affairs Medical Center, Portland, Oregon 97239, USAd
Address for correspondence: Klaus Früh or Ashlee V. Moses, 505 NW 185th Ave., Beaverton, OR 97006, USA. Voice: 503-418-2735; fax: 503-418-2701.
fruehk{at}ohsu.edu; mosesa{at}ohsu.edu
Ann. N.Y. Acad. Sci. 975: 180-191 (2002).
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.
Key Words: Kaposi's sarcoma-associated herpesvirus • microarray • c-kit • antisense
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