Crosstalk between the Androgen Receptor and PPAR Gamma Signaling Pathways in the Prostate

Figure 1

PPAR ligands regulate AR signaling within human prostate cancer cells. In AR-positive castration-sensitive prostate cancers such as LNCaP and VCaP cells (a), PPAR agonists and the PPAR antagonist GW9662 have been shown to decrease AR transcriptional activity. Agonist-induced reductions in AR signaling appear to occur independently of PPAR, while it is currently not known if PPAR is required for GW9662-induced reductions in AR activity. It is believed that these reductions in AR signaling contribute to the antiproliferative and antitumor effects of PPAR ligands in these early stage cancers. Conversely, PPAR agonists appear to enhance AR signaling via a PPAR1-dependent mechanism in the AR-positive, castration-resistant C4-2 cells (b). Data suggest that the antiproliferative effects of PPAR agonists in AR-positive cells do not require PPAR and appear to occur independently of any increases in AR activity within these cells. However, since AR activation can drive growth of castration-resistant tumors, it is possible PPAR agonist-induced increases in AR activity may interfere with the net ability of these compounds to reduce cell proliferation and tumor growth in AR-positive, castration-resistant cancers.

(a)

(b)