Comparative analysis of prostate-specific membrane antigen (PSMA) versus a prostate-specific membrane antigen-like gene.
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 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.


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.


CONCLUSIONS
The non-prostatic expression of PSMA should be taken into consideration when designing clinical strategies targeting PSMA.
O'Keefe
Denise S
DS
The Department of Urology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Bacich
Dean J
DJ
Heston
Warren D W
WD
D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics*; D001483:Base Sequence; D015152:Blotting, Northern; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D018076:DNA, Complementary; D015972:Gene Expression Regulation, Neoplastic; D043425:Glutamate Carboxypeptidase II / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007205:Indium Radioisotopes; D008297:Male; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D018076:DNA, Complementary; D007205:Indium Radioisotopes; C101315:Capromab Pendetide; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II