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Tissue expression and enzymologic characterization of human prostate specific membrane antigen and its rat and pig orthologs
Author(s) -
Rovenská Miroslava,
Hlouchová Klára,
Šácha Pavel,
Mlčochová Petra,
Horák Vratislav,
Zámečník Josef,
Bařinka Cyril,
Konvalinka Jan
Publication year - 2007
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20676
Subject(s) - glutamate carboxypeptidase ii , immunohistochemistry , western blot , prostate , biology , prostate cancer , monoclonal antibody , antigen , extracellular , pathology , microbiology and biotechnology , antibody , immunology , medicine , biochemistry , cancer , gene , genetics
BACKGROUND Prostate specific membrane antigen (PSMA), also called glutamate carboxypeptidase II (GCPII), is a target enzyme for diagnosis and treatment of prostate cancer. Moreover, it is upregulated in the vasculature of most solid tumors and is therefore a potential target for the generation of novel antineoplastics. In this context, we analyze the possibility of using rat and pig as animal models for enzymologic and in vivo studies. METHODS We prepared the recombinant extracellular part of human, rat, and pig GCPII in S2 cell media and characterized the activity and inhibition profiles of the three orthologs by radioenzymatic assay. We performed Western blot analysis of GCPII expression in human, rat, and pig tissues using the monoclonal antibody GCP‐04 and confirmed these findings by activity measurements and immunohistochemistry. RESULTS The three recombinant proteins show similar specific enzymatic activities and inhibition profiles. Tissue expression analysis revealed that most of the pig and human tissues show at least some GCPII‐positivity, while the expression pattern in rat is more restricted. Moreover, tissues such as prostate and testes exhibit different GCPII expression levels among the species studied. CONCLUSIONS The rat and pig orthologs of GCPII seem to be suitable to approximate human GCPII in enzymologic studies. However, the diffuse expression pattern of GCPII in animal and human tissues could be a caveat for the potential utilization of GCPII‐targeted anticancer drugs. Furthermore, variations in GCPII tissue distribution among the species studied should be considered when using rat or pig as models for antineoplastic drug discovery. Prostate 68: 171–182, 2008. © 2007 Wiley‐Liss, Inc.