O'Keefe Denise S, Bacich Dean J, Heston Warren D W
The Department of Urology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Prostate. 2004 Feb 1;58(2):200-10. doi: 10.1002/pros.10319.
Currently prostate-specific membrane antigen (PSMA) is showing promise both as an imaging and therapeutic target for occult prostate cancer metastases. First generation antibodies against PSMA are used for the FDA approved Prostascint trade mark monoclonal antibody scan and second generation antibodies are being developed for therapeutic targeting as well as imaging 1. However, there have been reports describing PSMA expression in non-prostatic tissues including kidney, liver, and brain. As we had previously showed the existence of a human PSMA homolog, we set out to determine if this non-prostatic expression was due to expression of the PSMA or another gene.
The PSMA homolog (PSMA-like) cDNA was cloned by screening a liver cDNA library. mRNA expression of the PSMA and PSMA-like genes was determined via Northern blot analysis using two different probes and protein expression confirmed in some tissues via Western blot analysis. Transcriptional regulation of the two genes was examined using reporter constructs driving luciferase expression.
The PSMA-like gene possesses 98% identity to the PSMA gene at the nucleotide level and is expressed in kidney and liver under the control of a different promoter to the PSMA gene. The PSMA gene is expressed in several human tissues and is most abundant in the nervous system and the prostate.
The non-prostatic expression of PSMA should be taken into consideration when designing clinical strategies targeting PSMA.
目前，前列腺特异性膜抗原（PSMA）作为隐匿性前列腺癌转移灶的成像和治疗靶点显示出前景。第一代抗PSMA抗体用于美国食品药品监督管理局（FDA）批准的Prostascint商标单克隆抗体扫描，第二代抗体正在开发用于治疗靶向以及成像。然而，有报道描述PSMA在包括肾脏、肝脏和大脑在内的非前列腺组织中表达。由于我们之前已证明人PSMA同源物的存在，我们着手确定这种非前列腺组织中的表达是由于PSMA还是另一个基因的表达所致。
通过筛选肝脏cDNA文库克隆PSMA同源物（PSMA样）cDNA。使用两种不同探针通过Northern印迹分析确定PSMA和PSMA样基因的mRNA表达，并通过Western印迹分析在某些组织中确认蛋白质表达。使用驱动荧光素酶表达的报告基因构建体检查这两个基因的转录调控。
PSMA样基因在核苷酸水平与PSMA基因具有98%的同一性，并且在与PSMA基因不同的启动子控制下在肾脏和肝脏中表达。PSMA基因在几种人体组织中表达，在神经系统和前列腺中最为丰富。
在设计针对PSMA的临床策略时，应考虑PSMA在非前列腺组织中的表达。
