Figure 6. Dependence of the MPAKT phenotype on mTOR is abrogated by MYC expression, and attenuated with age.
Prostates from mice aged 7 weeks, treated for 2 weeks with either vehicle or 10 mg/kg RAD001. H&E panels: RAD001 treatment fully reverts the mPIN phenotype in VP of 7-week-old MPAKT (n = 4–5/treatment group) - note reversion of nuclear atypia and re-polarization of basal nuclei. RAD001 treatment did not revert LP lesions in Hi-MYC (n = 6/treatment group) and in MPAKT/Hi-MYC (n = 5–6/treatment group) (H&E). IHC panels: Patchy pAKT expression remains detectable in reverted lesions of MPAKT mice, and in MPAKT/Hi-MYC, despite RAD001 treatment (see Fig. 3B for pAKT staining in vehicle-treated mice). pS6 is strongly expressed in areas of mPIN in VP of vehicle-treated MPAKT and reduced by RAD001 treatment. pS6 staining in LP of vehicle-treated Hi-MYC and MPAKT/Hi-MYC is patchy in mPIN. RAD001 treatment lowers but does not eliminate pS6 staining in Hi-MYC and MPAKT/Hi-MYC. Scale-bars: 50 µm (black), 100 µm (red).