SMAD3 and neoplasm: This suggests a model whereby ETV1 overexpression in the prostate in part limits its own oncogenic potential by activating the tumor suppressive power of TGF-β; but upon SMAD4 (or SMAD2 or SMAD3) downregulation or inactivating mutation, ETV1’s oncogenic activity becomes fully competent and this is needed for the progression of PIN to carcinoma in the prostate (Fig. 8).