Pten Dose Dictates Cancer Progression in the Prostate
Figure 6
Pten Dose Affects Prostate Tumor Progression
Pten+/− mice develop hyperplasia, dysplasia, and low-grade PIN. Ptenhy/− mice develop at complete penetrance high-grade PIN at a young age (8–10 wk) and roughly 25% present invasive CaP around 8 mo. Ptenpc mice develop invasive CaP at complete penetrance. (See Discussion for a detailed description.) p27Kip1−/− mice, on the contrary, develop only BPH. Possibilities for human therapeutic intervention derived from our findings: in addition to inactivation of PI3K/AKT and mTOR enzymatic activities (in PTEN loss of heterozygosity condition), monitoring and elevation of PTEN expression levels of the remaining allele could not only prevent formation of PIN lesions (in PTEN+/− individuals), but could importantly also be used to counteract the progression to invasive phenotypes (as observed in Ptenhy/− mouse mutants).