Comparative analysis of prostate-specific membrane antigen (PSMA) versus a prostate-specific membrane antigen-like gene
Comparative analysis of prostate-specific membrane antigen (PSMA) versus a prostate-specific membrane antigen-like gene
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DOI：
10.1002/pros.10319
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发表时间：
2004-02-01
期刊：
影响因子：
2.8
通讯作者：
Heston, WDW
中科院分区：
文献类型：
--
作者：
O'Keefe, DS;Bacich, DJ;Heston, WDW
背景。目前，前列腺特异性膜抗原（PSMA）作为隐匿性前列腺癌转移的影像学和治疗靶点显示出良好的前景。针对PSMA的第一代抗体用于FDA批准的Prostascint（TM）单克隆抗体扫描，第二代抗体正在开发用于治疗靶向和成像[1]。然而，有报道称PSMA在非前列腺组织中表达，包括肾、肝和脑。正如我们之前展示的人类PSMA同源物的存在一样，我们开始确定这种非前列腺表达是由于PSMA还是其他基因的表达。材料和方法。通过筛选肝脏cDNA文库，克隆PSMA同源（PSMA-like） cDNA。两种不同探针的Northern blot检测PSMA和PSMA样基因的mRNA表达，Western blot检测部分组织的蛋白表达。利用报告基因构建驱动荧光素酶表达，检测了这两个基因的转录调控。PSMA样基因在核苷酸水平上与PSMA基因具有98%的同源性，并在不同的启动子控制下在肾脏和肝脏中表达。PSMA基因在多种人体组织中均有表达，以神经系统和前列腺中表达量最多。在设计针对PSMA的临床策略时，应考虑PSMA的非前列腺表达。
BACKGROUND. 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(TM) 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.MATERIALS AND METHODS. 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.RESULTS. 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.CONCLUSION. The non-prostatic expression of PSMA should be taken into consideration when designing clinical strategies targeting PSMA.