Raf and VEGF: emerging therapeutic targets in Kaposi's sarcoma-associated herpesvirus infection and angiogenesis in hematopoietic and nonhematopoietic tumors.
Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with several cancers including Kaposi's sarcoma (KS), primary effusion lymphoma, and multicentric Castleman's disease. KSHV-mediated pathogenesis is dependent mainly on KSHV infection as well as on the microenvironment provided by the growth factors (GFs)/inflammatory cytokines (ICs). Recently, we determined that oncoprotein Raf enhances KSHV infection of target cells. Interestingly, Raf regulates the expression of a variety of GFs/ICs including those involved in angiogenesis such as vascular endothelial growth factor (VEGF). In this review, we discuss the effect of the Raf-GF/IC autocrine/paracrine loop on KSHV infection of both hematopoietic and nonhematopietic cells, and associated disease conditions.
Hamden
K E
KE
Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, 600 Moye Boulevard, Greenville, NC 27834, USA.
Whitman
A G
AG
Ford
P W
PW
Shelton
J G
JG
McCubrey
J A
JA
Akula
S M
SM
D006566:Herpesviridae Infections / Q000188:drug therapy*; D019288:Herpesvirus 8, Human / Q000472:pathogenicity*; D006801:Humans; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects* / Q000235:genetics; D048490:raf Kinases / Q000187:drug effects* / Q000235:genetics
D042461:Vascular Endothelial Growth Factor A; D048490:raf Kinases