Abstract
Currently no effective treatment is available for metastatic hormone refractory prostate cancer (HRPC). Hence, gene therapy represents a promising therapeutic strategy for such disease. In an attempt to develop an efficient and safe protocol to treat HRPC, we generated a highly augmented prostate specific two-step transcriptional amplification (TSTA) system to mediate targeted gene expression. Adenoviral vectors carrying the TSTA system (AdTSTA) exhibits activities that exceeds the CMV promoter while maintaining prostate specificity and androgen regulation in vivo (Sato et al. Mol Ther 2003, 8:726). The TSTA system consists of: 1) the GAL4-VP16 potent activator regulated by a modified PSA promoter/enhancer, and 2) a GAL4 responsive promoter driven transgene. TSTA activity critically relies on androgen receptor (AR) function. In this study, we aimed to determine the activity of AdTSTA in HRPC models such that future TSTA-based diagnostic and therapeutic applications can be utilized in this advanced disease.
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