HO-1 as a new player in prostate cancer progression.

VAZQUEZ E; GUERON G; FERRANDO M; ELGUERO B; SALLES A; MEISS R; COLOMBO L; NAVONE N; DE SIERVI A

Los cocos, Córdoba

Congreso; The First South American Spring Symposium in Signal Transduction and Molecular Medicine (SISTAM 2010); 2010

Prostate cancer (PCa) is the second leading cause of cancer-associated death in men. The metastatic spread of PCa cells and the ability to survive when reaching the metastatic nitch is affected by growth factors, angiogenic factors and hormones. Heme oxygenase-1 (HO-1) counteracts oxidative and inflammatory damage. Here we investigated its nuclear translocation in androgen sensitive and insensitive PCa cell lines. Our results showed that HO-1 overexpression induces its nuclear translocation. To understand HO-1 nuclear function, we analyzed its capacity to control androgen receptor (AR) targets. We found that HO-1 repressed the promoter activity of Prostate Specific Antigen (PSA), the best known AR downstream target and by ChIP we demonstrated that HO-1 associates to PSA promoter. HO-1 stable transfected PC3 cell lines (PC3HO-1) growing subcutaneously in athymic nude mice showed significant HO-1 nuclear staining. Using RT-qPCR-generated gene array we identified VEGFA as a novel downstream target of HO-1. An in vivo angiogenic assay also demonstrated that PC3HO-1 tumors presented less neovascularization than tumors derived from control cells. These results implicate for the first time HO-1 as a player in AR signaling and PCa progression.