title: Neutralizing VEGF bioactivity with a soluble chimeric VEGF-receptor protein flt(1-3)IgG inhibits testosterone-stimulated prostate growth in castrated mice.
abstract: BACKGROUND
  Recent studies show that testosterone-stimulated growth of the glandular tissue in the ventral prostate in adult castrated rats is preceded by increased epithelial VEGF synthesis, endothelial cell proliferation, vascular growth, and increased blood flow. These observations suggest that testosterone-stimulated prostate growth could be angiogenesis dependent, and that VEGF could play a central role in this process.
  
  
  METHODS
  Adult male mice were castrated and after 1 week treated with testosterone and vehicle, or with testosterone and a soluble chimeric VEGF-receptor flt(1-3)IgG protein.
  
  
  RESULTS
  Treatment with testosterone markedly increased endothelial cell proliferation, vascular volume, and organ weight in the ventral prostate lobe in the vehicle groups, but these responses were inhibited but not fully prevented by anti-VEGF treatment. The testosterone-stimulated increase in epithelial cell proliferation was unaffected by flt(1-3)IgG, but endothelial and epithelial cell apoptosis were increased in the anti-VEGF compared to the vehicle-treated groups.
  
  
  CONCLUSIONS
  This study suggests that testosterone stimulates vascular growth in the ventral prostate lobe indirectly by increasing epithelial VEGF synthesis and that this is a necessary component in testosterone-stimulated prostate growth.
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors.forename: Ingela Franck
authors.initials: IF
authors.lastname: Lissbrant
authors.forename: Peter
authors.initials: P
authors.lastname: Hammarsten
authors.forename: Erik
authors.initials: E
authors.lastname: Lissbrant
authors.forename: Napoleone
authors.initials: N
authors.lastname: Ferrara
authors.forename: Stina Häggström
authors.initials: SH
authors.lastname: Rudolfsson
authors.forename: Anders
authors.initials: A
authors.lastname: Bergh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002369:Castration; D002455:Cell Division / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007074:Immunoglobulin G / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000098:blood supply / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000008:administration & dosage*
chemical_list: D007074:Immunoglobulin G; D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D013739:Testosterone; D040281:Vascular Endothelial Growth Factor Receptor-1; D001973:Bromodeoxyuridine