Conditional PTEN-deficient Mice as a Prostate Cancer Chemoprevention Model


Background: We generated a mouse model of prostate cancer based on the adult-prostate-specific inactivationof phosphatase and tensin homolog (PTEN) using the Cre-loxP system. The potential of our mice as a useful animalmodel 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 μg/g of CMA threetimes a week for 9 or 14 weeks and sacrificed at weeks 15 and 20. Macroscopic change of the entire genitourinarytract (GUT) and histologically evident prostate gland tumor development were evaluated. Proliferation andapoptosis status in the prostate were examined by immunohistochemistry.
Results: CMA triggered significantshrinkage 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 prostateadenocarcinoma was not prevented but the proliferation of cancer cells was inhibited by CMA, which suggestedthe androgen axis is critical for cancer growth in these mice.
Conclusions: Conditional PTEN-deficient mice areuseful as a preclinical model for chemoprevention studies and serve as a valuable tool for the future screeningof potential chemopreventive agents.