The Kaposi’s Sarcoma-Associated Herpesvirus (KSHV/HHV-8) K1 Protein Induces Expression of Angiogenic and Invasion Factors
| Autor: | Stuart P. Krall, Blossom Damania, Joseph S. Pagano, Christine C. Tomlinson, Ling Wang, Naohiro Wakisaka, Scott M. DeWire |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cancer Research Angiogenesis viruses Transfection medicine.disease_cause Pathogenesis chemistry.chemical_compound Viral Envelope Proteins Gene expression medicine Humans Protein Isoforms Gammaherpesvirinae Secretion RNA Messenger Kaposi's sarcoma-associated herpesvirus Cells Cultured biology Membrane Proteins virus diseases Epithelial Cells biology.organism_classification medicine.disease Up-Regulation Vascular endothelial growth factor Matrix Metalloproteinase 9 Oncology chemistry Cancer research Fibroblast Growth Factor 2 Endothelium Vascular Primary effusion lymphoma |
| Zdroj: | Cancer Research. 64:2774-2781 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-03-3653 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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