In the current study, we sought to (1) establish a genetically engineered mouse model which recapitulates advanced prostate cancer due to prostate-specific MTA1 overexpression and the loss of PTEN expression (R26MTA1; Ptenf/f; Pb-Cre+, hereafter R26MTA1; Ptenf/f); (2) identify downstream pathways associated with an overexpression of MTA1 in PTEN-loss tumors and examine how these pathways contribute to the cooperative promotion of cancer progression; and (3) investigate the targeted efficacy of gnetin C on MTA1 downstream signaling in vivo. The gene discussed is PTEN; the disease is prostate carcinoma.