Expression pattern of mouse homolog of prostate-specific membrane antigen (FOLH1) in the transgenic adenocarcinoma of the mouse prostate model.
BACKGROUND
Prostate specific membrane antigen (PSMA) is expressed on the plasma membrane of normal prostate and in primary and metastatic prostate cancer in humans. Recently, a mouse homolog of PSMA (FOLH1) was identified that shares an 85% sequence homology with human PSMA. The transgenic adenocarcinoma of the mouse prostate (TRAMP) model displays spontaneous tumor development with age and metastasizes to tissues similar to human prostate cancer. This study characterized the expression of Folh1 in the TRAMP model to determine if the TRAMP would be a useful model system to evaluate PSMA-directed targeting strategies.


METHODS
A sensitive, real-time quantitative PCR assay was developed to measure Folh1 cRNA copy number in various tissues of 30-32-week-old TRAMP+ and age-matched, nontransgenic controls (TRAMP-).


RESULTS
Of the tissues studied, the highest expression of Folh1 was observed in the kidney and brain of both TRAMP+ and TRAMP- mice. Low levels of Folh1 cRNA (1-2 copies/ng total RNA) were detected in the tumor and lymph nodes of TRAMP+ mice and in the seminal vesicles and lung of the TRAMP+ and TRAMP- mice. The expression of Folh1 mRNA was sixfold higher in the prostate of 32-week-old TRAMP- mice compared to the tumor of 32-week-old TRAMP+ mice. The rank order of the Folh1 expression in the tissues studied was kidney > brain > prostate > tumor > lymph nodes > lung > seminal vesicles > liver. Folh1 mRNA was undetectable in the bone marrow of both TRAMP+ and TRAMP- mice. Folate hydrolase activity assayed in the kidney, brain, lung, and liver paralleled the expression of Folh1 mRNA in these tissues.


CONCLUSIONS
We demonstrate that Folh1 is expressed at very high levels in some normal mouse tissues including the prostate gland and that the expression is not upregulated in the tumor of 32-week-old TRAMP+ mice.
Schmittgen
Thomas D
TD
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, Washington, USA. Schmittgen@dendrite.pharmacy.ohio-state.edu
Zakrajsek
Brian A
BA
Hill
Richard E
RE
Liu
Qian
Q
Reeves
Jerry J
JJ
Axford
Paul D
PD
Singer
Michael J
MJ
Reed
Michael W
MW
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000818:Animals; D002268:Carboxypeptidases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D043425:Glutamate Carboxypeptidase II; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012334:RNA, Neoplasm; D002268:Carboxypeptidases; D043425:Glutamate Carboxypeptidase II