Vascular endothelial growth factor up-regulates cyclooxygenase-2 expression in human endothelial cells.
Journal Article (Journal Article)
We investigated the effects of vascular endothelial growth factor (VEGF) on cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) (PGE(2)) synthesis in human microvascular endothelial cells (HMEC-1). Treatment of HMEC-1 with VEGF resulted in a dose- and time-dependent up-regulation of COX-2 mRNA and protein levels. This up-regulation was accompanied by a 1.6-fold increase in PGE(2) synthesis. Pretreatment of HMEC-1 with a selective COX-2 inhibitor, NS-398, abolished VEGF-induced PGE(2) synthesis, suggesting specific up-regulation of COX-2 activity by VEGF in HMEC-1. Transient transfection assays using deletion mutants of the human COX-2 promoter fused to the luciferase reporter gene indicated critical requirement of a regulatory region spanning -828/-123 bp for VEGF induction of COX-2 promoter activity in HMEC-1. Site-directed mutation analysis demonstrated that a GATA cis-acting element at -685/-680 bp was essential for VEGF- induced COX-2 promoter activity in HMEC-1. These observations are of particular importance given the recent demonstrations of critical requirement of COX-2 isoenzyme for tumor growth and angiogenesis.
Full Text
Duke Authors
Cited Authors
- Tamura, M; Sebastian, S; Gurates, B; Yang, S; Fang, Z; Bulun, SE
Published Date
- July 2002
Published In
Volume / Issue
- 87 / 7
Start / End Page
- 3504 - 3507
PubMed ID
- 12107271
International Standard Serial Number (ISSN)
- 0021-972X
Digital Object Identifier (DOI)
- 10.1210/jcem.87.7.8796
Language
- eng
Conference Location
- United States