Pten Dose Affects Prostate Tumor Progression

<p><i>Pten</i>^+/− mice develop hyperplasia, dysplasia, and low-grade PIN. <i>Pten</i>^hy/− mice develop at complete penetrance high-grade PIN at a young age (8–10 wk) and roughly 25% present invasive CaP around 8 mo. <i>Pten</i>^pc mice develop invasive CaP at complete penetrance. (See Discussion for a detailed description.) <i>p27^Kip1−/−</i> 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 <i>PTEN</i> loss of heterozygosity condition), monitoring and elevation of PTEN expression levels of the remaining allele could not only prevent formation of PIN lesions (in <i>PTEN</i>^+/− individuals), but could importantly also be used to counteract the progression to invasive phenotypes (as observed in <i>Pten</i>^hy/−<i></i>mouse mutants).