Use of the PSA enhancer core element to modulate the expression of prostate- and non-prostate-specific basal promoters in a lentiviral vector context

S. Chapel-Fernandes, F. Jordier, F. Lauro, N. Maitland, J. Chiaroni, P. de Micco, P. Mannoni, C. Bagnis

Research output: Contribution to journalArticlepeer-review

Abstract

\Composite promoters combining the prostate-specific antigen (PSA) enhancer core element with promoter elements derived from gene coding for human prostate-specific transglutaminase gene, prostate-specific membrane antigen gene, prostate-specific antigen, rat probasin or phosphoglycerate kinase were characterized for their ability to specifically express the enhanced green fluorescent protein (EGFP) gene in prostate versus non-prostate cancer cell lines when transferred with a human immunodeficiency virus-1-based lentiviral vector. By themselves minimal proximal promoter elements were found to inefficiently promote relevant tissue-specific expression; in all the vectors tested, addition of the PSA enhancer core element markedly improved EGFP expression in LnCaP, a cancer prostate cell line used as a model for prostate cancer. The composite promoter was inactive in HuH7,a hepatocarcinoma cell line used as a model of neighboring non-prostate cancer cells. Among the promoters tested, the combination of the PSA enhancer and the rat probasin promoter showed both high specificity and a strong EGFP expression. Neither a high viral input nor the presence of the cPPT/CTS sequence affected composite promoter behavior. Our data suggest that composite prostate-specific promoters constructed by combining key elements from various promoters can improve and/or confer tissue specific expression in a lentiviral vector context.

Original languageEnglish
Pages (from-to)919-929
Number of pages11
JournalCancer gene therapy
Volume13
Issue number10
DOIs
Publication statusPublished - Oct 2006

Keywords

  • lentiviral vector
  • prostate cancer
  • specific expression
  • PSA
  • TISSUE-SPECIFIC EXPRESSION
  • TUMOR-ASSOCIATED NEOVASCULATURE
  • VIVO GENE DELIVERY
  • CENTRAL DNA FLAP
  • MEMBRANE ANTIGEN
  • IN-VIVO
  • REGULATED EXPRESSION
  • PROBASIN GENE
  • EFFICIENT TRANSDUCTION
  • TRANSGLUTAMINASE GENE

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