title: Use of the PSA enhancer core element to modulate the expression of prostate- and non-prostate-specific basal promoters in a lentiviral vector context.
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.
authors.affiliation: EFS Alpes Méditerranée, Marseille, France.
authors.forename: S
authors.initials: S
authors.lastname: Chapel-Fernandes
authors.forename: F
authors.initials: F
authors.lastname: Jordier
authors.forename: F
authors.initials: F
authors.lastname: Lauro
authors.forename: N
authors.initials: N
authors.lastname: Maitland
authors.forename: J
authors.initials: J
authors.lastname: Chiaroni
authors.forename: P
authors.initials: P
authors.lastname: de Micco
authors.forename: P
authors.initials: P
authors.lastname: Mannoni
authors.forename: C
authors.initials: C
authors.lastname: Bagnis
mesh_terms: D045744:Cell Line, Tumor; D004742:Enhancer Elements, Genetic; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000378:metabolism*; D017430:Prostate-Specific Antigen / Q000235:genetics*
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D017430:Prostate-Specific Antigen