title: Exposure to hypoxia following irradiation increases radioresistance in prostate cancer cells.
abstract: BACKGROUND
  Tumor hypoxia is a common feature of prostate tumors associated with the stabilization of hypoxia-inducible-factor 1alpha (HIF-1α) and poor prognosis following radiation therapy. Lack of oxygen at the time of irradiation is associated with radioresistance, but recent reports suggest radioresponse is also modulated by the dynamic nature of tumor hypoxia.
  
  
  OBJECTIVE
  We proposed to evaluate the effect of post-irradiation hypoxic exposure on the radioresponse of 2 prostate cancer (CaP) cell lines (22Rv1, DU145) and to examine whether it correlates with modified cellular responses induced by hypoxia.
  
  
  RESULTS
  Aerobic and hypoxic CaP cells exposed to hypoxia (24 h) after irradiation (4 Gy) gained a survival advantage compared with cells fully oxygenated after irradiation. This survival advantage was associated with induction of a G2/M cell cycle arrest, reduced induction of apoptosis and decreased amount of senescent cells. These modified cellular responses appeared mediated by HIF-1α.
  
  
  CONCLUSIONS
  Our data suggest that targeting hypoxia after irradiation may benefit patients with aggressive hypoxic prostate tumors.
authors: Prostate Molecular Oncology Group, Academic Unit of Clinical and Molecular Oncology, Trinity College, Dublin, Ireland; Department of Urology, St James's Hospital, Dublin, Ireland.
authors: Derek
authors: D
authors: Hennessey
authors: Lynn M
authors: LM
authors: Martin
authors: Anne
authors: A
authors: Atzberger
authors: Thomas H
authors: TH
authors: Lynch
authors: Donal
authors: D
authors: Hollywood
authors: Laure
authors: L
authors: Marignol
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D015153:Blotting, Western; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D016922:Cellular Senescence / Q000528:radiation effects*; D005434:Flow Cytometry; D059565:G2 Phase Cell Cycle Checkpoints / Q000528:radiation effects*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A