Prostate-specific suicide gene therapy using the prostate-specific membrane antigen promoter and enhancer.

摘要: BACKGROUND Prostate-specific membrane antigen (PSMA) is abundantly expressed in virtually 100% of prostate cancers and metastases. In addition, unlike prostate-specific (PSA), PSMA upregulated under conditions androgen deprivation. Therefore, an attractive therapeutic target for advanced cancer. Recently, both the promoter enhancer driving expression gene were cloned. We describe here our analysis most active region(s) present a way using combination with E. coli cytosine deaminase suicide-driven therapy that converts nontoxic prodrug 5-fluorocytosine (5-FC) into cytotoxic drug 5-fluorouracil (5-FU) cancer cells. METHODS Deletion constructs full-length subcloned luciferase reporter vector containing either or SV-40 promoter. The portion was then determined via activity C4-2 cell line. replaced subclone showed activity. specificity this technique examined vitro, line LNCaP, its androgen-independent derivative C4-2, number nonprostatic lines. toxicity 5-FC 5-FU on transiently transfected lines compared. RESULTS The region originally isolated from approximately 2 kb. Deletion revealed at least two distinct regions seem to contribute cells, therefore best construct be 1,648 bp long. IC50 similar all tested (>10 mM). However, transfection 1648 nt drive enhanced dose-dependent manner more than 50-fold, while cells did not express significantly sensitized by transfection. CONCLUSIONS Suicide may benefit patients who have undergone ablation are suffering relapse disease. Prostate 45:149–157, 2000. © 2000 Wiley-Liss, Inc.