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Conditional PTEN-deficient Mice as a Prostate Cancer Chemoprevention Model

  • Koike, Hiroyuki (Department of Urology, Kinki University Faculty of Medicine) ;
  • Nozawa, Masahiro (Department of Urology, Kinki University Faculty of Medicine) ;
  • De Velasco, Marco A (Department of Urology, Kinki University Faculty of Medicine) ;
  • Kura, Yurie (Department of Urology, Kinki University Faculty of Medicine) ;
  • Ando, Naomi (Department of Urology, Kinki University Faculty of Medicine) ;
  • Fukushima, Emiko (Department of Urology, Kinki University Faculty of Medicine) ;
  • Yamamoto, Yutaka (Department of Urology, Kinki University Faculty of Medicine) ;
  • Hatanaka, Yuji (Department of Urology, Kinki University Faculty of Medicine) ;
  • Yoshikawa, Kazuhiro (Cell Therapy Center, Aichi Medical University) ;
  • Nishio, Kazuto (Department of Genome Biology, Kinki University Faculty of Medicine) ;
  • Uemura, Hirotsugu (Department of Urology, Kinki University Faculty of Medicine)
  • Published : 2015.03.18

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). Materials and Methods: Six-week-old mice were treated subcutaneously with $50{\mu}g/g$ 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.

Keywords

Animal model;chlormadinone acetate;prevention;prostate cancer;PTEN

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