title: p53 status is a major determinant of effects of decreasing peroxiredoxin I expression on tumor growth and response of lung cancer cells to treatment.
abstract: OBJECTIVE
  The potential roles of peroxiredoxin (Prx) I in carcinogenesis and treatment have been explored. Our previous study revealed differences between A549 (functional p53) and H1299 (null p53) Prx I antisense transfectants. The discrepancy might have resulted from the p53 status. In this study, we further investigated the role of Prx I and p53 on lung cancer growth and the response to treatment in vitro and in vivo.
  
  
  METHODS
  We established stable A549 and H1299 transfectants with Prx I antisense and p53, respectively. We then examined their characteristics in vitro and used nude mice xenografts of these cell lines to compare their capacity for tumor invasion and spontaneous metastasis and their sensitivity to radiotherapy.
  
  
  RESULTS
  Increased reactive oxygen species caused by lower Prx I activity induced p53 expression. In lethal stress, the augmentation of reactive oxygen species was partially reversed by blocking p53 in A549 with Prx I antisense. We demonstrated the potential contribution of p53-dependent mechanisms to inhibit lung tumor growth and increase radiosensitization using H1299 transfected with p53 in vitro and in vivo. An increased p53 level attenuated the capacity of the cells for metastasis by decreasing vascular endothelial growth factor and induced radiosensitization by increased apoptosis and cell senescence and by regulating intracellular reactive oxygen species.
  
  
  CONCLUSIONS
  These results suggest that p53 status has an important role in the tumor-inhibiting and radiosensitizing effects of decreasing Prx I. Both Prx I and p53 may be powerful prognosticators for lung cancer.
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital, Putz City, Chia-Yi Hsien, Taiwan. miaofen@adm.cgmh.org.tw
authors.forename: Miao-Fen
authors.initials: MF
authors.lastname: Chen
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Chen
authors.forename: Chun-Te
authors.initials: CT
authors.lastname: Wu
authors.forename: Paul-Yang
authors.initials: PY
authors.lastname: Lin
authors.forename: Hungyi
authors.initials: H
authors.lastname: Shau
authors.forename: Shuen-Kuei
authors.initials: SK
authors.lastname: Liao
authors.forename: Cheng-Ta
authors.initials: CT
authors.lastname: Yang
authors.forename: Kuan-Der
authors.initials: KD
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D004249:DNA Damage; D016158:Genes, p53 / Q000235:genetics; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins; D011836:Radiation Tolerance; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*; D001616:beta-Galactosidase / Q000032:analysis
chemical_list: D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C024829:8-hydroxyguanine; D006147:Guanine; D010544:Peroxidases; D054464:Peroxiredoxins; D001616:beta-Galactosidase