AbstractBACKGROUNDCurrently 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™ 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 METHODSThe 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.RESULTSThe 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.CONCLUSIONThe non‐prostatic expression of PSMA should be taken into consideration when designing clinical strategies targeting PSMA. © 2003 Wiley‐Liss, Inc.