SPA-mediated inhibition of the proliferation of PCa cells is caused by AR-dependent transcriptional mechanisms involving the repression of the transcription factors that underlie cell growth (e.g., c-MYC, E2F)35, the upregulation of cell-cycle inhibitors (e.g., p27, p21, Skp2)73,74, the induction of terminal differentiation (e.g., APRIN, PLZF)75–80, the repression of DNA replication genes81, the repression of AR and AR variants37,81,82, and activation of cell senescence through the repression of E2F-regulated genes36,39. This evidence concerns the gene SKP2 and posterior cortical atrophy.