Titre du document / Document title

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

Auteur(s) / Author(s)

TAMURA Mitsutoshi ; SEBASTIAN Siby ; GURATES Bilgin ; SIJUN YANG ; ZONGJUAN FANG ; BULUN Serdar E. ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

Departments of Obstetrics and Gynecology and Molecular Genetics, The University of Illinois at Chicago, Chicago, IL 60612, ETATS-UNIS

Résumé / Abstract

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.

Revue / Journal Title

The Journal of clinical endocrinology and metabolism   ISSN 0021-972X   CODEN JCEMAZ 

Source / Source

2002, vol. 87, n^o7, pp. 3504-3507 (19 ref.)

Langue / Language

Anglais

Editeur / Publisher

Endocrine Society, Bethesda, MD, ETATS-UNIS  (1952) (Revue)

Mots-clés anglais / English Keywords

Enzyme ; Oxidoreductases ; In vitro ; Human ; Angiogenesis ; Biosynthesis ; Prostaglandin E2 ; Enzymatic activity ; Gene expression ; Prostaglandin-endoperoxide synthase ; Microcirculation ; Blood vessel ; Endothelial cell ; Biological activity ; Vascular endothelium growth factor ;

Mots-clés français / French Keywords

Enzyme ; Oxidoreductases ; In vitro ; Homme ; Angiogenèse ; Biosynthèse ; Prostaglandine E2 ; Activité enzymatique ; Expression génique ; Prostaglandin-endoperoxide synthase ; Microcirculation ; Vaisseau sanguin ; Cellule endothéliale ; Activité biologique ; Facteur croissance endothélium vasculaire ;

Mots-clés espagnols / Spanish Keywords

Enzima ; Oxidoreductases ; In vitro ; Hombre ; Angiogénesis ; Biosíntesis ; Prostaglandina E2 ; Actividad enzimática ; Expresión genética ; Prostaglandin-endoperoxide synthase ; Microcirculación ; Vaso sanguíneo ; Célula endotelial ; Actividad biológica ; Factor crecimiento endotelio vascular ;

Localisation / Location

INIST-CNRS, Cote INIST : 6022, 35400010884568.0770