Bjerke and co-workers found that inactivation of TGF-β signaling by the deletion of the TGF-β type II receptor gene in combination with Pten KO led to enhanced malignancy [40], suggesting that TGF-β signaling in the prostate epithelial cells has tumor suppressor function in Pten KO mice during prostate cancer development. This evidence concerns the gene PTEN and Familial prostate cancer.