1. ¹EFS Alpes Méditerranée, Marseille, France
2. ²Prostate Cancer: Initiative for Gene Therapy (PIG), YCR Cancer Research Unit, Department of Biology (Area 13), University of York Heslington, York, UK

Correspondence: Dr C Bagnis, EFS Alpes Méditerranée, 149 Bd Baille, Marseille na 13005, France. E-mail: claude.bagnis@gmail.com

Received 23 September 2005; Revised 22 January 2006; Accepted 26 March 2006; Published online 2 June 2006.

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.