Prostate stem cell antigen enhancer and uroplakin II promoter based bladder cancer targeted tissue-specific vector

被引:19
作者
Wang, Degui [1 ,2 ]
Wang, Zhiping [1 ]
Tian, Junqiang [1 ]
He, Xiangdong [1 ]
Chowdhury, Wasim H. [3 ]
Zhang, Xiangbo [1 ]
Li, Shigang [1 ]
Rodriguez, Ronald [3 ]
机构
[1] Lanzhou Univ, Hosp 2, Inst Urol, Lanzhou 730000, Peoples R China
[2] Lanzhou Univ, Sch Basic Med Sci, Lanzhou 730000, Peoples R China
[3] Johns Hopkins Univ, Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA
关键词
Prostate stem cell antigen enhancer; Uroplakin II promoter; Gene therapy; Bladder cancer; GENE-EXPRESSION; PANCREATIC ADENOCARCINOMA; ONCOLYTIC ADENOVIRUS; CARCINOMA; IDENTIFICATION; IMMUNOTHERAPY; MARKERS; TRIAL;
D O I
10.1016/j.urolonc.2008.02.002
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: To construct a dual specific vector which contains prostate stem cell antigen enhancer (PSCAE) and uroplakin II (UPII) promoter targeted bladder cancer. Methods: UPII promoter and PSCAE were amplified by polymerase chain reaction (PCR). Luciferase gene (LUC) was obtained from plasmid pBK-CMV-LUC. PSCAE. UPII promoter and LUC were inserted into shuttle plasmid to create Rp-UPII-LUC and Rp-PSCAE-UPII-LUC. Rp-UPII-LUC and Rp-PSCAE-UPII-LUC were cotransfected with pCMV-beta-gal into various cell lines at the presence or absence of androgen receptor agonist R1881 and androgen receptor antagonist flutamide. Luminescence was detected with luciferase assay kit and counted on liquid scintillation counter. Results: Bladder cancer cells showed higher LUC activity than non-bladder cancer cells after transfected with plasmids Rp-UPII-LUC and Rp-PSCAE-UPII-LUC. PSCAE could improve the LUC activity in both AR positive and AR negative bladder cancer cells but not in non-bladder cancer cells and normal human urothelial (NHU) cells. R1881 could increase the LUC activity in AR positive bladder cancer cells but not in AR negative bladder cancer cells and non-bladder cancer cells. Flutamide could not inactivate PSCAE in bladder cancer cells. Conclusions: PSCAE can improve target gene expression in bladder cancer cells but not in non-bladder cancer cells and NHU cells. PSCAE maintains a certain level of androgen independent activity in bladder cancer cells. PSCAE is active in both AR positive and AR negative bladder cancer cells. The results suggest that combination of PSCAE with UPII promoter is feasible in constructing bladder cancer-specific vectors. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:164 / 169
页数:6
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