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A Functional Genomics Approach to Kaposi's Sarcoma
Author(s) -
MOSES ASHLEE V.,
JARVIS MICHAEL A.,
RAGGO CAMILO,
BELL YOLANDA C.,
RUHL REBECCA,
LUUKKONEN B.G. MATTIAS,
GRIFFITH DIANA J.,
WAIT CECILY L.,
DRUKER BRIAN J.,
HEINRICH MICHAEL C.,
NELSON JAY A.,
FRÜH KLAUS
Publication year - 2002
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2002.tb05951.x
Subject(s) - carcinogenesis , biology , angiogenesis , kaposi's sarcoma , kaposi's sarcoma associated herpesvirus , cancer research , sarcoma , oncogene , receptor tyrosine kinase , microarray analysis techniques , cell , virology , virus , gene , gene expression , cell cycle , microbiology and biotechnology , signal transduction , pathology , genetics , medicine , herpesviridae , human herpesvirus , viral disease
A bstract : 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.