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nature portfolio yen-hung chow & shen pang permissions reprints privacy policy nature advertising social media egfp-positive lncap cells author information authors prostate-specific antigen gene development reducing fgf-2-mediated angiogenesis prostate-specific vector carrying egfp-positive control cells prostate-specific antigen expression hsv-tk/gcv approach author correspondence phr′-cmv-egfp plasmids enhancer expressing tissue-specificity sustained long-term expression cancer gene therapy personal data cancer gene ther prostate-specific antigen prostate specific antigen prostate cancer prostate cell lines derived springerlink instant access data protection shen pang permissions gene driven metastatic prostate cancer human immunodeficiency virus huvec cell line eradicating cancer cells protein–protein interaction hormone therapy prior efficacious gene vector highly tissue specific tissue-specific expression prostate-specific targeting egfp lentiviral vector neoadjuvant hormonal therapy cre-mediated excision tumour cell surface control cells carried prostate cancer patients article yu nonspecific viral promoters

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         description:The prostate-specific antigen (PSA) promoter is known to be highly tissue specific. Although its tissue specificity has been confirmed, its efficiency of gene transcription is significantly lower compared to known nonspecific viral promoters. These lower levels of promoter activity therefore pose a problem when developing an efficacious gene vector for prostate cancer gene therapy. Thus, selecting an appropriate therapeutic gene and vector system to carry the gene driven by the PSA promoter (PSAP) is important. In the studies described here, a human immunodeficiency virus (HIV)-1–based lentiviral vector carrying either the enhanced green fluorescent protein (EGFP) reporter or the diphtheria toxin A (DTA) gene was constructed. The results demonstrate that the PSA promoter in a lentiviral vector drives genes in prostate cells with satisfactory efficacy and specificity. The tissue-specific expression of the DTA protein efficiently eradicates LNCaP prostate cells in culture. We also infected prostate cancer cells and control cells carried by nude mice with the EGFP lentiviral vector. Significant numbers of EGFP-positive LNCaP cells were detected in all the mice bearing these tumors, but no EGFP-positive control cells were detected in any other mouse tissue. The high levels of expression in prostate cells, compared with the low levels of background expression in other cells, show that the PSAP-lentiviral vector could be a potential useful tool for gene therapy of metastatic prostate cancer. Cancer Gene Therapy (2001) 8, 628–635.
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