1. ¹Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China
2. ²Department of Obstetrics and Gynecology, Ren Ji Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
3. ³Department of Obstetrics and Gynecology, University of Wisconsin-Madison, 7 East-Meriter Hospital, Madison, WI, USA
4. ⁴Department of Urology, West China Hospital, SiChuan University, Chengdu, China

Correspondence: Professor H Li, Department of Urology, West China Hospital, SiChuan University, No 17, 3 duan RenMin South Road, Chengdu 610041, China. E-mail: drlihong2000@yahoo.com; Professor SJ Xia, Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China. E-mail: xsjurologist@163.com

⁵These authors contributed equally to this work.

Received 10 April 2008; Revised 22 May 2008; Accepted 16 June 2008; Published online 15 July 2008.

Abstract

This study was designed to investigate the prostate cancer-specific tumoricidal effect of the suicide gene, Escherichia coli uracil phosphoribosyltransferase (UPRT), driven by the human prostate-specific membrane antigen promoter/enhancer (PSMA_E/P) in vitro. When transfected with PSMA_E/P-EGFP (enhanced green fluorescence protein) (a plasmid construct with the green fluorescence protein gene driven by the PSMA_E/P), only the androgen-responsive and PSMA-positive prostate cancer cell line, LNCaP, expressed GFP, indicating the specificity of the PSMA_E/P activity in androgen-sensitive and PSMA-positive prostate cancer cells. Taking advantage of this prostate cancer-specific property of PSMA_E/P, we successfully introduced bacterial UPRT into LNCaP cells where the tumoricidal effect of 5-fluorouracil (5-FU) was significantly increased when compared with the cells without the exogenous UPRT. We conclude that the efficacy of 5-FU-based chemotherapy in prostate cancers can be significantly improved by targeted expression of the suicide gene UPRT under the control of PSMA_E/P.