title: HIF2 alpha reduces growth rate but promotes angiogenesis in a mouse model of neuroblastoma.
abstract: BACKGROUND
  HIF2alpha/EPAS1 is a hypoxia-inducible transcription factor involved in catecholamine homeostasis, vascular remodelling, physiological angiogenesis and adipogenesis. It is overexpressed in many cancerous tissues, but its exact role in tumour progression remains to be clarified.
  
  
  METHODS
  In order to better establish its function in tumourigenesis and tumour angiogenesis, we have stably transfected mouse neuroblastoma N1E-115 cells with the native form of HIF2alpha or with its dominant negative mutant, HIF2alpha (1-485) and studied their phenotype in vitro and in vivo.
  
  
  RESULTS
  In vitro studies reveal that HIF2alpha induces neuroblastoma cells hypertrophy and decreases their proliferation rate, while its inactivation by the HIF2alpha (1-485) mutant leads to a reduced cell size, associated with an accelerated proliferation. However, our in vivo experiments show that subcutaneous injection of cells overexpressing HIF2alpha into syngenic mice, leads to the formation of tumour nodules that grow slower than controls, but that are well structured and highly vascularized. In contrast, HIF2alpha (1-485)-expressing neuroblastomas grow fast, but are poorly vascularized and quickly tend to extended necrosis.
  
  
  CONCLUSIONS
  Together, our data reveal an unexpected combination between an antiproliferative and a pro-angiogenic function of HIF2alpha that actually seems to be favourable to the establishment of neuroblastomas in vivo.
authors.affiliation: Research Center, Montreal Heart Institute, Montreal, Québec, Canada. judith.favier@college-de-france.fr
authors.forename: Judith
authors.initials: J
authors.lastname: Favier
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lapointe
authors.forename: Ricardo
authors.initials: R
authors.lastname: Maliba
authors.forename: Martin G
authors.initials: MG
authors.lastname: Sirois
mesh_terms: D020533:Angiogenesis Inhibitors / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D020533:Angiogenesis Inhibitors; D051792:Basic Helix-Loop-Helix Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1