Vascular endothelial growth factor up-regulates cyclooxygenase-2 expression in human endothelial cells

Mitsutoshi Tamura, Siby Sebastian, Bilgin Gurates, Sijun Yang, Zongjuan Fang, Serdar E. Bulun*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


We investigated the effects of vascular endothelial growth factor (VEGF) on cycloxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) 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 PGE2 synthesis. Pretreatment of HMEC-1 with a selective COX-2 inhibitor, NS-398, abolished VEGF-induced PGE2 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.

Original languageEnglish (US)
Pages (from-to)3504-3507
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Issue number7
StatePublished - 2002

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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