The Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) K1 protein induces expression of angiogenic and invasion factors.
Cancer Res
; 64(8): 2774-81, 2004 Apr 15.
Article
en En
| MEDLINE
| ID: mdl-15087393
Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) has been linked to Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. In addition to endothelial cells and B lymphocytes, KSHV also has been shown to infect epithelial cells and keratinocytes. The transmembrane glycoprotein K1, encoded by the first open reading frame of KSHV, is a signaling protein capable of eliciting B-cell activation. We show that KSHV K1 can induce expression and secretion of vascular endothelial growth factor (VEGF) in epithelial and endothelial cells. Up-regulation of VEGF was mediated at the transcriptional level because expression of K1 resulted in VEGF promoter activation. We also show that K1 induces expression of matrix metalloproteinase-9 (MMP-9) in endothelial cells. Additional analyses with K1 mutant proteins revealed that the SH2 binding motifs present in the K1 cytoplasmic tail are necessary for VEGF secretion and MMP-9 induction. These results indicate that K1 signaling may contribute to KSHV-associated pathogenesis through a paracrine mechanism by promoting the secretion of VEGF and MMP-9 into the surrounding matrix.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas del Envoltorio Viral
/
Factor 2 de Crecimiento de Fibroblastos
/
Factor A de Crecimiento Endotelial Vascular
/
Proteínas de la Membrana
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Cancer Res
Año:
2004
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos