Comparative study of PSMA expression in the prostate of mouse, dog, monkey, and human

被引:37
作者
Aggarwal, Saurabh
Ricklis, Rebecca M.
Williams, Simon A.
Denmeade, Samuel R.
机构
[1] Johns Hopkins Univ, Dept Chem & Biomol Engn, Whiting Sch Engn, Baltimore, MD USA
[2] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA
关键词
PSMA; monkey; primate; dog; toxicology;
D O I
10.1002/pros.20413
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
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. METHOD. PSMA enzymatic activity and protein expression was determined. PSMA expression in the prostates of mouse, dog, and monkey were compared to humans by realtime 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.
引用
收藏
页码:903 / 910
页数:8
相关论文
共 26 条
[1]
Anilkumar G, 2003, CANCER RES, V63, P2645
[2]
Bacich Dean J., 2002, Proceedings of the American Association for Cancer Research Annual Meeting, V43, P312
[3]
Cloning, expression, genomic localization, and enzymatic activities of the mouse homolog of prostate-specific membrane antigen/NAALADase/folate hydrolase [J].
Bacich, DJ ;
Pinto, JT ;
Tong, WP ;
Heston, WDW .
MAMMALIAN GENOME, 2001, 12 (02) :117-123
[4]
Immunological and inflammatory characterisation of three canine cell lines: K1, K6 and DH82 [J].
Barnes, A ;
Bee, A ;
Bell, S ;
Gilmore, W ;
Mee, A ;
Morris, R ;
Carter, SD .
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 2000, 75 (1-2) :9-25
[5]
Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase [J].
Carter, RE ;
Feldman, AR ;
Coyle, JT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (02) :749-753
[6]
Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase [J].
Davis, MI ;
Bennett, MJ ;
Thomas, LM ;
Bjorkman, PJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (17) :5981-5986
[7]
Prostate-specific antigen-activated thapsigargin prodrug as targeted therapy for prostate cancer [J].
Denmeade, SR ;
Jakobsen, CM ;
Janssen, S ;
Khan, SR ;
Garrett, ES ;
Lilja, H ;
Christensen, SB ;
Isaacs, JT .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2003, 95 (13) :990-1000
[8]
Gao J, 2001, CANCER RES, V61, P5038
[9]
Folylpoly-γ-glutamate carboxypeptidase from pig jejunum -: Molecular characterization and relation to glutamate carboxypeptidase II [J].
Halsted, CH ;
Ling, EH ;
Luthi-Carter, R ;
Villanueva, JA ;
Gardner, JM ;
Coyle, JT .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (32) :20417-20424
[10]
Anti-tumor effects and lack of side effects in mice of an immunotoxin directed against human and plouse prostate-specific membrane antigen [J].
Huang, XM ;
Bennett, M ;
Thorpe, PE .
PROSTATE, 2004, 61 (01) :1-11