Reference SummaryVoelkel-Johnson C, Carcinogenesis 2000 Aug;21(8):1623-7

Title

Genomic instability-based transgenic models of prostate cancer.

Authors

Voelkel-Johnson C; Voeks DJ; Greenberg NM; Barrios R; Maggouta F; Kurtz DT; Schwartz DA; Keller GM; Papenbrock T; Clawson GA; Norris JS

Journal

Carcinogenesis

Volume

21

Issue

8

Year

2000

Pages

1623-7

Abstract

To develop animal models that represent the broad spectrum of human prostate cancer, we created transgenic mice with targeted prostate-specific expression of two genes (ECO:RI and c-fos) implicated in the induction of genomic instability. Expression of the transgenes was restricted to prostate epithelial cells by coupling them to the tissue-specific, hormonally regulated probasin promoter (PB). The effects of transgene expression were examined histologically in prostate sections at time points taken from 4 to 24 months of age. The progressive presence of regions of mild-to-severe hyperplasia, low- and high-grade prostatic intra-epithelial neoplasia, and well-differentiated adenocarcinoma was observed in both PBECO:RI lines but no significant pathology was detected in the PBfos line. Prostate tissue of PBECO:RI mice was examined for expression of p53, proliferating cell nuclear antigen (PCNA) and Ki67 at multiple time points. Although p53 does not appear to be mutated, levels of PCNA and Ki67 are elevated and correlate with the severity of the prostatic lesions. Overall, pre-neoplastic and neoplastic stages represented in the PBECO:RI model showed similarity to corresponding early stages of the human disease. This genomic instability-based model will be used to study the mechanisms involved in the early stages of prostate carcinogenesis and to investigate the nature of subsequent events necessary for the progression to advanced disease.

Links

10910968 – National Library of Medicine/PubMed

Strain Notes

Strain Note
[not specified]-Tg(PBEcoRI)#Jsn Two single-copy transgenic lines were produced (22L, 25N). It is not clear which one was carried in these mice.

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
[not specified]-Tg(PBEcoRI)#Jsn Prostate gland adenocarcinoma Prostate gland

observed

[not specified]-Tg(PBEcoRI)#Jsn Prostate gland hyperplasia Prostate gland

observed

[not specified]-Tg(PBEcoRI)#Jsn Prostate gland prostatic intraepithelial neoplasia - low grade (LGPIN) Prostate gland

observed

[not specified]-Tg(PBfos)38Jsn Prostate gland prostatic intraepithelial neoplasia - low grade (LGPIN) Prostate gland

observed

FVB Prostate gland prostatic intraepithelial neoplasia - low grade (LGPIN) Prostate gland

observed