title: REG4, NEIL2, and BIRC5 gene expression correlates with gamma-radiation sensitivity in patients with rectal cancer receiving radiotherapy.
abstract: OBJECTIVE
  The present study aimed to identify genes that influence the susceptibility of cancer cells to radiation.
  
  
  METHODS
  The sensitivities of eight colorectal cancer cell lines to gamma radiation were tested. Microarray data and cells with stable overexpression were used to identify candidate genes. Candidate genes correlating with radioresistance were validated with the use of 22 clinical specimens obtained before preoperative radiotherapy from patients with rectal cancer.
  
  
  RESULTS
  Regenerating islet-derived protein 4 (REG4) gene expression was 12-fold higher in radioresistant cells. REG4-overexpressing cells had higher survival rates and fewer DNA strand breaks after gamma irradiation. Expression of the antiapoptotic gene baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) and base excision-repair pathway gene nei endonuclease VIII-like 2 (NEIL2) in REG4-overexpressing cells, was also three to four times higher than that of the parental cell lines. REG4, BIRC5 and NEIL2 expression levels were significantly higher in non-responding patients (n=14) than in responders (n=8).
  
  
  CONCLUSIONS
  The REG4, BIRC5 and NEIL2 genes might be useful predictors of the sensitivity of cancer patients to radiotherapy.
authors.affiliation: Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan. azteca_tk@yahoo.co.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobunai
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Toshio
authors.initials: T
authors.lastname: Fukusato
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D020552:Comet Assay; D045647:DNA Glycosylases / Q000096:biosynthesis*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000096:biosynthesis*; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000235:genetics; D005720:Gamma Rays; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis*; D037181:Lectins, C-Type / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D000073718:Pancreatitis-Associated Proteins; D011836:Radiation Tolerance / Q000235:genetics; D011878:Radiotherapy / Q000379:methods; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C428528:REG4 protein, human; D000077022:Survivin; D043224:Deoxyribonuclease (Pyrimidine Dimer); D045647:DNA Glycosylases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; C473642:NEIL2 protein, human