Novel Prostate-Specific Promoter Derived from PSA and PSMA Enhancers

• DOI: 10.1006/mthe.2002.0682
• Publication Date: 2002-09-25T18:55:31Z
• Authors: Sang-Jin Lee; Hong-Sup Kim; Rong Yu; KangRyul Lee; Thomas A. Gardner; Chaeyong Jung; Meei-Huey Jeng; Fan Yeung; Liang Cheng; Chinghai Kao
• Keywords: Glutamate carboxypeptidase II

The expression of prostate-specific membrane antigen (PSMA) and (PSA), two well characterized marker proteins, remains highly active in the hormone refractory stage prostate cancer. In this study, an artificial chimeric enhancer (PSES) composed modified regulatory elements controlling PSA PSMA genes was tested for its promoter activity tissue specificity using reporter system. As a result, novel PSES remained silent PSA- PSMA-negative non-prostate cancer cell lines, but mediated high levels luciferase PSMA-expressing lines presence absence androgen. To determine whether could be used vivo gene therapy cancer, recombinant adenovirus, Ad-PSES-luc, constructed. Luciferase by Ad-PSES-luc 400- to 1000-fold higher than several other suggesting tissue-specificity adenoviral vector. Finally, virus injected into mice evaluate tissue-discriminatory experimental animal. Unlike Ad-CMV-luc, from systemic injection fairly low all major organs. However, when prostate, drove almost exclusively not tissues. Our results demonstrated potential use treatment androgen-independent patients.