Abstract
Abstract : The overall goal of of our proposal is to develop a new transgenic model of prostate cancer by targeting transformation to prostatic basal cells using the PSCA promoter. Major Findings: A 9kb region upstream of the PSCA coding region was isolated and demonstrated to drive prostate-specific expression in vitro. This region was subsequently tested in vivo using a GFP reporter construct. Analysis of these mice showed the GFP expression was almost exclusively localized to the prostate. GFP expression in these mice was regulated developmentally, with prominent expression localized to the ductal tips of the prostate. Promoter activity was both responsive to androgen and independent of androgen. Recently we have tried to use this promoter to target expression of oncogenes to the prostate. Multiple attempts have failed to produce founders. Analysis of PSCA and GFP expression during embryogenesis showed that PSCA is expressed in multiple peithelial tissues in utero. Conclusion: The PSCA promoter can target a subset of prostate epithelial cells in vivo, but inducible forms of the promoter may be necessary to deliver oncogenes to these cells.
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