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Abstract

The utility of the promoter/enhancer region (i.e. regulatory region) of the PSP94 gene in targeting expression of heterologous genes, to the prostate gland was analyzed. Three breeding lines (i.e., line A, line B and line C) of the PSP-TGMAP model described herein were established with constructs containing regulatory regions with or without additional exon/intron sequence of the PSP94 gene. These regulatory regions were operatively linked to the simian virus 40 (SV40) T antigen (Tag, including both the large T and small t antigens). Histopathology evaluation of tumor grade, transgene expression, tumor responsiveness to androgen deprivation and tumor metastatic potential were analyzed and reported herein. This study indicates that regulatory regions (e.g., the promoter/enhancer with exon/intron region) of the PSP94 gene efficiently target the expression of heterologous genes to prostate tissue. Furthermore, the PSP-TGMAP model provides a valuable tool for the analysis of prostate cancer development and for developing new gene therapy vector for the treatment of prostate cancer. Based on this study, mouse PSP94 promoter/enhancer region may be used in the generation of a 'shuttle vector' fit for prostate targeting in both mouse CaP model and in human clinical trial.

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