2002
DOI: 10.1128/jvi.76.16.8383-8399.2002
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Kaposi's Sarcoma-Associated Herpesvirus-Induced Upregulation of the c-kitProto-Oncogene, as Identified by Gene Expression Profiling, Is Essential for the Transformation of Endothelial Cells

Abstract: Kaposi's sarcoma (KS),Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) (or human herpesvirus 8) is consistently associated with all epidemiologic forms of KS and is recognized as the etiologic agent of the disease (15,27). Within the KS lesion, KSHV infects the spindle-shaped cells that characterize the tumor as well as their endothelial cell precursors (15,62,100). The majority of infected cells harbor the KSHV genome in a latent form, with a small percentage entering a lytic cycle and producing infectious… Show more

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Cited by 136 publications
(149 citation statements)
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“…Efficient KSHV infection was confirmed by high levels of expression of LANA mRNA in infected HDMECs. We found that 3-7% of infected HDMECs were ORF59-positive and 1.5-3% were K8.1 positive, in agreement with previous results [12][13][14] . This indicates that <10% of the cells were undergoing lytic reactivation.…”
supporting
confidence: 81%
“…Efficient KSHV infection was confirmed by high levels of expression of LANA mRNA in infected HDMECs. We found that 3-7% of infected HDMECs were ORF59-positive and 1.5-3% were K8.1 positive, in agreement with previous results [12][13][14] . This indicates that <10% of the cells were undergoing lytic reactivation.…”
supporting
confidence: 81%
“…The IR joins a growing list of host cell proteins essential for the transformed phenotype in ECs infected by KSHV in vitro (Moses et al, 2002;McAllister et al, 2004;Raggo et al, 2005). It seems that multiple mechanisms are required to support the postconfluent growth of DMVEC.…”
Section: Discussionmentioning
confidence: 99%
“…Upon infection with KSHV, E-DMVECs develop a spindle cell phenotype, lose contact inhibition, form foci when cultured postconfluence and acquire the ability to form colonies in soft agar. The E-DMVEC system has thus been extremely useful for evaluating changes in the cellular transcriptome and proteome, ultimately leading to the identification of both known as well as novel oncogenes that are likely to be involved in KS tumorigenesis (Moses et al, 2002;McAllister et al, 2004;Raggo et al, 2005).…”
Section: Introductionmentioning
confidence: 99%
“…Transcriptional profiling of cultured endothelial cells infected with KSHV in vitro has identified several cellular genes that are strongly upregulated by KSHV infection and which may contribute to the increased proliferation, the loss of contact inhibition, and the differentiation stage of KSHVinfected endothelial cells. Thus, the receptor tyrosine kinase c-kit is strongly up-regulated in KSHVinfected DMVECs [78,79]; its ligand, stem cell factor (SCF), enhances the growth of KSHV-infected DMVECs; and a small molecule inhibitor of c-kit, STI 571 ('Gleevec'), inhibits the morphological changes induced by KSHV in DMVECs [78]. Other cellular genes induced by KSHV include the orphan chemokine receptor RDC1 and neuritin, a protein previously linked to neurite outgrowth [80].…”
Section: The Role Of Kshv In the Development Of Kaposi's Sarcomamentioning
confidence: 99%
“…Suppression of RDC1 and neuritin gene expression by antisense oligonucleotides or siRNA reversed the morphological changes and increased proliferation induced by KSHV in DMVECs and also the growth in soft agar and tumourigenicity in the nude mouse model of 3T3 mouse fibroblasts stably transfected with either RDC1 or neuritin [80]. Haem oxygenase 1 (HO-1) is among several other cellular genes induced in cultured endothelial cells by latent KSHV infection [78][79][80][81][82][83] and is also expressed in KSHV-infected spindle cells in KS lesions [83]. The HO-1 inhibitor chromium mesoporphyrin IX inhibits haem-induced proliferation of KSHV-infected, but not uninfected, DMVECs, suggesting a role for HO-1 in the proliferation of KSHV-infected spindle cells [83].…”
Section: The Role Of Kshv In the Development Of Kaposi's Sarcomamentioning
confidence: 99%