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Specific targeting of prostate cancer cells in vitro by the suicide gene/prodrug system, uracil phosphoribosyltransferase/5-fluorouracil, under the control of prostate-specific membrane antigen promoter/enhancer

Prostate Cancer and Prostatic Diseases volume 12, pages 166–171 (2009)Cite this article

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 (PSMAE/P) in vitro. When transfected with PSMAE/P-EGFP (enhanced green fluorescence protein) (a plasmid construct with the green fluorescence protein gene driven by the PSMAE/P), only the androgen-responsive and PSMA-positive prostate cancer cell line, LNCaP, expressed GFP, indicating the specificity of the PSMAE/P activity in androgen-sensitive and PSMA-positive prostate cancer cells. Taking advantage of this prostate cancer-specific property of PSMAE/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 PSMAE/P.

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Acknowledgements

We thank Hao Zeng for providing plasmid of pPSMAE/P-EGFP. This study was funded by the Science and Technology Bureau of SiChuan province in China for Scientific Research (04JY029-082-1).

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Author notes

  1. F J Zhao and S Zhang: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China

    F J Zhao & S J Xia

  2. Department of Obstetrics and Gynecology, Ren Ji Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

    S Zhang

  3. Department of Obstetrics and Gynecology, University of Wisconsin-Madison, 7 East-Meriter Hospital, Madison, WI, USA

    Z M Yu

  4. Department of Urology, West China Hospital, SiChuan University, Chengdu, China

    H Li

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  1. F J Zhao
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  2. S Zhang
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  5. H Li
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Correspondence to S J Xia or H Li.

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Zhao, F., Zhang, S., Yu, Z. et al. Specific targeting of prostate cancer cells in vitro by the suicide gene/prodrug system, uracil phosphoribosyltransferase/5-fluorouracil, under the control of prostate-specific membrane antigen promoter/enhancer. Prostate Cancer Prostatic Dis 12, 166–171 (2009). https://doi.org/10.1038/pcan.2008.39

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