title: Conditional PTEN-deficient mice as a prostate cancer chemoprevention model.
abstract: BACKGROUND
  We generated a mouse model of prostate cancer based on the adult-prostate-specific inactivation of phosphatase and tensin homolog (PTEN) using the Cre-loxP system. The potential of our mice as a useful animal model was examined by evaluating the chemopreventive efficacy of the anti-androgen, chlormadinone acetate (CMA).
  
  
  METHODS
  Six-week-old mice were treated subcutaneously with 50 μg/g of CMA three times a week for 9 or 14 weeks and sacrificed at weeks 15 and 20. Macroscopic change of the entire genitourinary tract (GUT) and histologically evident prostate gland tumor development were evaluated. Proliferation and apoptosis status in the prostate were examined by immunohistochemistry.
  
  
  RESULTS
  CMA triggered significant shrinkage of not only the GUT but also prostate glands at 15 weeks compared to the control (p=0.017 and p=0.010, respectively), and the trend became more marked after a further five-weeks of treatment. The onset of prostate adenocarcinoma was not prevented but the proliferation of cancer cells was inhibited by CMA, which suggested the androgen axis is critical for cancer growth in these mice.
  
  
  CONCLUSIONS
  Conditional PTEN-deficient mice are useful as a preclinical model for chemoprevention studies and serve as a valuable tool for the future screening of potential chemopreventive agents.
authors.affiliation: Department of Urology, Kinki University Faculty of Medicine, Osaka, Japan E-mail : nozawa06@med.kindai.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koike
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nozawa
authors.forename: Marco A
authors.initials: MA
authors.lastname: De Velasco
authors.forename: Yurie
authors.initials: Y
authors.lastname: Kura
authors.forename: Naomi
authors.initials: N
authors.lastname: Ando
authors.forename: Emiko
authors.initials: E
authors.lastname: Fukushima
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hatanaka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Uemura
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018890:Chemoprevention; D002715:Chlormadinone Acetate / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D014566:Urogenital System / Q000166:cytology / Q000473:pathology
chemical_list: D000726:Androgen Antagonists; D016588:Anticarcinogenic Agents; D002715:Chlormadinone Acetate; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse