Characterization of SV-40 Tag rats as a model to study prostate cancer.
BACKGROUND
Prostate cancer is the second most frequently diagnosed cancer in men. Animal models that closely mimic clinical disease in humans are invaluable tools in the fight against prostate cancer. Recently, a Simian Virus-40 T-antigen (SV-40 Tag) targeted probasin promoter rat model was developed. This model, however, has not been extensively characterized; hence we have investigated the ontogeny of prostate cancer and determined the role of sex steroid receptor and insulin-like growth factor-1 (IGF-1) signaling proteins in the novel SV-40 Tag rat.


METHODS
The SV-40 Tag rat was histopathologically characterized for time to tumor development, incidence and multiplicity and in the ventral, dorsal, lateral and anterior lobes of the prostate. Immunoassay techniques were employed to measure cell proliferation, apoptosis, and sex steroid receptor and growth factor signaling-related proteins. Steroid hormone concentrations were measured via coated well enzyme linked immunosorbent assay (ELISA) kits.


RESULTS
Prostatic intraepithelial neoplasia (PIN) and well-differentiated prostate cancer developed as early as 2 and 10 weeks of age, respectively in the ventral prostate (VP) followed by in the dorsolateral (DLP). At 8 weeks of age, testosterone and dihydrotestosterone (DHT) concentrations in SV-40 Tag rats were increased when compared to non-transgenic rats. High cell proliferation and apoptotic indices were found in VP and DLP of transgenic rats. Furthermore, we observed increased protein expression of androgen receptor, IGF-1, IGF-1 receptor, and extracellular signal-regulated kinases in the prostates of SV-40 Tag rats.


CONCLUSIONS
The rapid development of PIN and prostate cancer in conjunction with the large prostate size makes the SV-40 Tag rat a useful model for studying prostate cancer. This study provides evidence of the role of sex steroid and growth factor proteins in prostate cancer development and defines appropriate windows of opportunity for preclinical trials and aids in the rational design of chemoprevention, intervention, regression, and therapeutic studies using prostate cancer rodent models.
Harper
Curt E
CE
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama, USA. charper@uab.edu
Patel
Brijesh B
BB
Cook
Leah M
LM
Wang
Jun
J
Shirai
Tomoyuki
T
Eltoum
Isam A
IA
Lamartiniere
Coral A
CA
D000367:Age Factors; D000727:Androgen-Binding Protein; D000818:Animals; D000952:Antigens, Polyomavirus Transforming; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004958:Estradiol / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D009363:Neoplasm Proteins / Q000097:blood; D011230:Precancerous Conditions / Q000097:blood / Q000473:pathology / Q000821:virology; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology / Q000821:virology; D051381:Rats; D013539:Simian virus 40 / Q000276:immunology*; D013739:Testosterone / Q000031:analogs & derivatives / Q000097:blood; D013997:Time Factors
D000727:Androgen-Binding Protein; D000952:Antigens, Polyomavirus Transforming; D009363:Neoplasm Proteins; C027519:probasin; D013739:Testosterone; D004958:Estradiol; C013915:boldenone; D007334:Insulin-Like Growth Factor I