The protective effect of cGMP activation against breast tumor progression was mostly explained by the induction of apoptotic pathways through the activation of caspase-3 and -9, PKG-induced β-catenin phosphorylation and ubiquitination, the down-regulation of oncogenes and anti-apoptotic genes (e.g., cyclin D1, c-myc, survivin), and the inhibition of PDE5. This evidence concerns the gene PDE5A and breast neoplasm.