title: Progestins activate vascular endothelial growth factor gene transcription in endometrial adenocarcinoma cells.
abstract: OBJECTIVE
  To determine whether progestins activate vascular endothelial growth factor (VEGF) gene transcription in endometrial adenocarcinoma cells.
  
  
  METHODS
  In vitro study.
  
  
  METHODS
  University reproductive biology laboratories.
  
  
  METHODS
  None.
  
  
  METHODS
  Ishikawa cells were transfected with VEGF promoter-luciferase reporter constructs and expression vectors encoding human progesterone receptors (hPR) A or B. The cells were treated with different progestins and antiprogestins, and luciferase activity was compared with controls.
  
  
  METHODS
  Three functional progesterone response elements (PREs) in the VEGF promoter were identified by electrophoretic mobility-shift assay, and different constructs were created to assess each PRE.
  
  
  RESULTS
  In cells expressing hPRA or B, treatment with 10 nM R5020 or 100 nM medroxyprogesterone acetate statistically significantly increased luciferase activity (3.3- to 4.8-fold). Pretreatment with 100 nM RU486 blunted the effect of 10 nM R5020, resulting only in a slight, statistically nonsignificant increase in luciferase activity (1.3- to 1.7-fold). Although three different functional PREs could be identified, no single PRE accounted for the preponderance of the luciferase activity. Full VEGF promoter activation required all three PREs.
  
  
  CONCLUSIONS
  Progestins have a direct effect on VEGF gene transcription. However, hPR-mediated transcriptional regulation of the VEGF promoter is complex and cannot be localized to confined PRE sequences. Other response element motifs are likely to play a contributory role.
authors.affiliation: Department of Obstetrics and Gynecology, Inselspital, University of Bern, Bern, Switzerland. michel.mueller@insel.ch
authors.forename: Michael D
authors.initials: MD
authors.lastname: Mueller
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Vigne
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Pritts
authors.forename: Victor
authors.initials: V
authors.lastname: Chao
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Dreher
authors.forename: Robert N
authors.initials: RN
authors.lastname: Taylor
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics*; D016228:Endothelial Growth Factors / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008222:Lymphokines / Q000235:genetics*; D008525:Medroxyprogesterone / Q000494:pharmacology*; D015735:Mifepristone / Q000494:pharmacology*; D011397:Promegestone / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D011980:Receptors, Progesterone; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015735:Mifepristone; D011397:Promegestone; D008525:Medroxyprogesterone