Figure 4

Working model for COUP-TFII function in prostate tumorigenesis. PTEN inactivation results in an increase of COUP-TFII expression in prostate cancer cells, which will consequently promote tumor growth through the regulation of cell cycle or growth related genes such as E2F1, Cyclin A, Cyclin B and etc. In addition, further increase in COUP-TFII expression in prostate cancer constrains the TGF-β-dependent growth barrier through direct association with Smad4, thereby downregulating p21 expression and enhancing Cyclin D1 expression. In summary, COUP-TFII serves as an important regulator to control PTEN-mediated prostate tumorigenesis and renders the indolent tumors to acquire metastatic potential through destruction of the TGF-β-dependent growth barrier.