SMAD3 and Familial prostate cancer: However, in contradiction to this hypothesis, we observed no alteration of SMAD3/4 protein levels in PC3 prostate cancer cells upon ETV1 downregulation (see Fig. 5) or in RWPE-1 cells upon ETV1 overexpression (see Fig. 4a); this has the caveat that PC3 and RWPE-1 cells are of human and not mouse origin and that in vitro cell culture does not always mimic a complex organ such as the prostate.