Abstract
BackgroundProstate 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.MethodsThe 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.ResultsProstatic 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.ConclusionThe 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.
Highlights
Prostate cancer is the second most frequently diagnosed cancer in men
Histopathology Via the ontogeny study, we found that precursor lesion and prostate tumor progression was more rapid in the ventral prostate (VP) than the dorsolateral prostate (DLP) of SV-40 Simian Virus large T antigen (Tag) rats (Table 1)
In the VP and DLP of 12 week old SV40 Tag rats, we found that protein expression of ER-alpha was significantly down-regulated by approximately 50% compared to the VP and DLP of non-transgenic rats
Summary
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. A Simian Virus-40 T-antigen (SV-40 Tag) targeted probasin promoter rat model was developed This model, has not been extensively characterized; 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. Prostate cancer is the second most frequently diagnosed cancer in men, with 782,600 new cases projected to occur in 2007 [1]. Whether or not elevated blood levels of androgens are a significant risk factor for prostate cancer is open for debate. Some have reported that increased testosterone levels in the blood are associated with an increased risk of prostate cancer [4]. Others have failed to support the "androgen hypothesis" that circulating testosterone and DHT are positively associated with prostate cancer risk [5]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call