Comparative study of PSMA expression in the prostate of mouse, dog, monkey, and human.
BACKGROUND
Intraprostatic PSMA targeted prodrugs/protoxins are under development in our laboratory. Future toxicologic studies of these therapies require identification of animal models that express PSMA within the prostate.


METHODS
PSMA enzymatic activity and protein expression was determined. PSMA expression in the prostates of mouse, dog, and monkey were compared to humans by real-time PCR analysis.


RESULTS
No substrate hydrolysis was observed in dog or monkey prostate homogenates. Monkey prostate was negative for PSMA protein expression. No significant PSMA mRNA levels were detected by real time PCR in mouse, dog, or monkey prostate tissue compared to PSMA negative tissues.


CONCLUSIONS
PSMA is not expressed in any significant amount in the prostates of mouse, beagle dog, or macaque monkeys in this study but is expressed in high levels by human prostate. These non-human species, therefore, are not suitable toxicologic models to assess prostate damage from PSMA-activated intraprostatic prodrug/protoxin therapies.
Aggarwal
Saurabh
S
Department of Chemical and Biomolecular Engineering, The Johns Hopkins University Whiting School of Engineering, Baltimore, Maryland 21231, USA.
Ricklis
Rebecca M
RM
Williams
Simon A
SA
Denmeade
Samuel R
SR
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis* / Q000235:genetics*; D015153:Blotting, Western; D004195:Disease Models, Animal; D004285:Dogs; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology*; D043425:Glutamate Carboxypeptidase II / Q000032:analysis* / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D011467:Prostate / Q000737:chemistry*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018675:Toxicity Tests
D000954:Antigens, Surface; D012333:RNA, Messenger; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II