NOS3 and Familial prostate cancer: Previously, we demonstrate that eNOS exhibits an increased immunoexpression pattern in both high-grade hormone-naïve and hormone-refractory (castration-failed and castration-plus-flutamide-failed) prostate cancer samples and also activated eNOS-NO signaling can function to promote the antiandrogen-resistant growth of prostate cancer cells via a mechanism of NO-mediated suppression of AR activity [27].