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.
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).
Zhao
F J
FJ
Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Zhang
S
S
Yu
Z M
ZM
Xia
S J
SJ
Li
H
H
D000954:Antigens, Surface / Q000235:genetics*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004742:Enhancer Elements, Genetic; D004926:Escherichia coli / Q000235:genetics; D005434:Flow Cytometry; D005472:Fluorouracil / Q000627:therapeutic use*; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D043425:Glutamate Carboxypeptidase II / Q000235:genetics*; D049452:Green Fluorescent Proteins; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010430:Pentosyltransferases / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D000954:Antigens, Surface; D000970:Antineoplastic Agents; D049452:Green Fluorescent Proteins; D010430:Pentosyltransferases; C023269:uracil phosphoribosyltransferase; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D005472:Fluorouracil