B-Raf-dependent expression of vascular endothelial growth factor-A in Kaposi sarcoma-associated herpesvirus-infected human B cells
Autor: | Audy G. Whitman, Khalief E. Hamden, Benjaman A. Bryan, James A. McCubrey, Shaw M. Akula, Patrick W. Ford, Paul P. Cook |
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Rok vydání: | 2005 |
Předmět: |
MAPK/ERK pathway
Proto-Oncogene Proteins B-raf Vascular Endothelial Growth Factor A Angiogenesis viruses Immunology Biochemistry Cell Line medicine Gammaherpesvirinae Humans Extracellular Signal-Regulated MAP Kinases B-Lymphocytes biology Neovascularization Pathologic MEK inhibitor virus diseases Cell Biology Hematology Herpesviridae Infections biochemical phenomena metabolism and nutrition biology.organism_classification medicine.disease Vascular endothelial growth factor A Gene Expression Regulation Cell culture Herpesvirus 8 Human Cancer research Primary effusion lymphoma Endothelium Vascular Signal transduction Signal Transduction |
Zdroj: | Blood. 105(11) |
ISSN: | 0006-4971 |
Popis: | Kaposi sarcoma–associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) is etiologically linked to Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease. Vascular endothelial growth factor–A (VEGF-A) is one of the essential factors required in KSHV pathogenesis, mainly due to its ability to mediate angiogenesis. In this report we analyzed the relationship between Raf and VEGF-A expression in KSHV-infected hematopoietic cells. All of the KSHV-infected cell lines (derived from PEL) expressed higher levels of B-Raf and VEGF-A when compared with uninfected cells. Inhibition of Raf to mitogen-induced extracellular kinase (MEK) to extracellular signal-related kinase (ERK) signaling, either by the use of MEK inhibitor (PD98059) or by siRNA specific to B-Raf, significantly lowered VEGF-A expression. In addition, B-Raf–induced VEGF-A expression was demonstrated to be sufficient to enhance tubule formation in endothelial cells. Interestingly, we did not observe mutation in the B-Raf gene of the KSHV-infected PEL cell lines. Taken together, we report for the first time the ability of Raf-associated signaling to play a role in the expression of VEGF-A in KSHV-infected hematopoietic cells. |
Databáze: | OpenAIRE |
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