Rodriguez R, Schuur E R, Lim H Y, Henderson G A, Simons J W, Henderson D R
Brady Urological Institute, Johns Hopkins University Oncology Center, Baltimore, Maryland 21287, USA.
Cancer Res. 1997 Jul 1;57(13):2559-63.
Prostate-specific antigen (PSA) is a widely used marker for the diagnosis and management of prostate cancer. Minimal enhancer/promoter constructs derived from the 5' flank of the human PSA gene (prostate-specific enhancer) were inserted into adenovirus type 5 DNA so as to drive the E1A gene, thereby creating a prostate-specific enhancer-containing virus, CN706. E1A was expressed at high levels in CN706-infected human PSA-producing LNCaP cells but not in CN706-infected DU145 cells, which are human prostate cells that do not express PSA. The titer of CN706 was significantly higher in LNCaP cells compared to several human cell lines that do not produce PSA (HBL100, PANC-1, MCF-7, DU145, and OVCAR3). Furthermore, in LNCaP cells, the yield of CN706 was dependent on exogenous androgen (R1881). CN706 destroyed large LNCaP tumors (1 x 10(9) cells) and abolished PSA production in nu/nu mouse xenograft models with a single intratumoral injection.
前列腺特异性抗原（PSA）是一种广泛用于前列腺癌诊断和治疗的标志物。将源自人PSA基因5'侧翼的最小增强子/启动子构建体（前列腺特异性增强子）插入5型腺病毒DNA中，以驱动E1A基因，从而创建一种含前列腺特异性增强子的病毒CN706。E1A在感染CN706的人PSA产生细胞LNCaP中高水平表达，但在感染CN706的DU145细胞中不表达，DU145细胞是不表达PSA的人前列腺细胞。与几种不产生PSA的人类细胞系（HBL100、PANC-1、MCF-7、DU145和OVCAR3）相比，CN706在LNCaP细胞中的滴度显著更高。此外，在LNCaP细胞中，CN706的产量依赖于外源性雄激素（R1881）。在裸鼠异种移植模型中，单次瘤内注射CN706可破坏大的LNCaP肿瘤（1×10⁹个细胞）并消除PSA的产生。
