Characterization of Prostate-Specific Membrane Antigen (PSMA) for Use in Therapeutic and Diagnostic Strategies Against Prostate Cancer

Abstract : Prostate-Specific Membrane Antigen (PSMA) appears to be an ideal prostate cancer marker and potential therapeutic target, however there have been reports of PSMA expression in non-prostatic tissues, including brain, kidney and liver. Such expression of PSMA could weaken the potential of the gene as a prostate cancer marker or at least produce confusing and conflicting data. Prior to this project, we had demonstrated that there was another human gene, 97% identical to PSMA, which we termed the PSMA-Like gene. The first aim of this project was to characterize the differences between the non-prostatic and prostatic forms of PSMA and to determine strategies to specifically target PSMA expressed in prostate or prostate tumors. The second aim of the project was to define the minimal regulatory regions of the PSMA gene, for future utilization in gene therapy strategies, by analyzing deletion constructs of the gene regulatory regions. To date we have cloned and characterized the PSMA-Like gene, and determined ways of distinguishing the two genes at the DNA, RNA and protein levels which will aid in designing new diagnostic and therapeutic anti-prostate cancer strategies. In addition, we have characterized the promoter and enhancer region of PSMA, and developed gene therapy vectors that specifically kill human prostate cancer tumors growing in mice.