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.
Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, 600 Moye Boulevard, Greenville, NC 27834, USA.
K E
KE
Hamden
A G
AG
Whitman
P W
PW
Ford
J G
JG
Shelton
J A
JA
McCubrey
S M
SM
Akula
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