RGD Reference Report - Characterization of SV-40 Tag rats as a model to study prostate cancer. - Rat Genome Database

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Characterization of SV-40 Tag rats as a model to study prostate cancer.

Authors: Harper, CE  Patel, BB  Cook, LM  Wang, J  Shirai, T  Eltoum, IA  Lamartiniere, CA 
Citation: Harper CE, etal., BMC Cancer. 2009 Jan 26;9:30.
RGD ID: 2306713
Pubmed: PMID:19171036   (View Abstract at PubMed)
PMCID: PMC2639608   (View Article at PubMed Central)
DOI: DOI:10.1186/1471-2407-9-30   (Journal Full-text)

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. CONCLUSION: 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prostate carcinoma in situ  ISOIgf1 (Rattus norvegicus)2306713; 2306713protein:increased expression:prostate glandRGD 
prostate carcinoma in situ  IEP 2306713protein:increased expression:prostate glandRGD 
Prostatic Neoplasms  ISOIgf1 (Rattus norvegicus)2306713; 2306713protein:increased expression:prostate glandRGD 
Prostatic Neoplasms  IEP 2306713protein:increased expression:prostate glandRGD 

Objects Annotated

Genes (Rattus norvegicus)
Igf1  (insulin-like growth factor 1)

Genes (Mus musculus)
Igf1  (insulin-like growth factor 1)

Genes (Homo sapiens)
IGF1  (insulin like growth factor 1)


Additional Information