University of Mississippi Medical Center Jackson United States
The goal of this project is to elucidate MTA1-mediated anticancer efficacy of pterostilbene PTER. For this, PC3M prostate cancer cells which express high levels of MTA1 were transduced with lentiviral MTA1shRNA and cells were characterized in functional assays. Cells were also tagged with luciferase to be utilized in vivo for monitoring tumor growth in live animals. We also examined the effects of PTER on PTEN expression in DU145 cells in vitro and in DU145-senografts. ChIP experiments showed that MTA1 can directly bind VEGF promoter. We completed experiments with Pten-null mice, in which we demonstrated MTA1-mediated anticancer effects of PTER. Treatment efficacy was determined by examining disease severity and pathology H and E and IHC, tissue and serum accumulation of pterostilbene by GC-MS, changes in molecular targets by qRT-PCR and western blots. We showed that high levels of MTA1 in Pten-lossprostate cooperate with key oncogenes, including c-Myc and Akt among others, to promote prostate cancer progression. In addition, loss-of-function studies using human prostate cancer cells indicated direct involvement of MTA1 in inducing inflammation and EMT.