Reference SummaryShibata MA, Cancer Res 1996 Nov 1;56(21):4894-903

Title

Progression of prostatic intraepithelial neoplasia to invasive carcinoma in C3(1)/SV40 large T antigen transgenic mice: histopathological and molecular biological alterations.

Authors

Shibata MA; Ward JM; Devor DE; Liu ML; Green JE

Journal

Cancer Res

Volume

56

Issue

21

Year

1996

Pages

4894-903

Abstract

The progression of prostatic intraepithelial neoplasia (PIN) to invasive prostate carcinoma has been analyzed in the C3(1)/T(AG) transgenic mouse model and appears very similar to the process proposed to occur in humans. PIN lesions in these transgenic mice histologically resemble those found in human PIN. Low-grade PIN was observed in the ventral and dorsolateral lobes at 2 months of age, whereas high-grade PIN was found in both lobes by 5 months of age. A progressive increase in the number of PIN lesions was observed with age. Prostate carcinomas, which appeared to arise from PIN lesions, were found by 7 months of age in the ventral lobe and 11 months of age in the dorsolateral lobe. Expression of T(AG) mRNA and protein in these lesions correlated with the development of PIN and carcinomas, as did the overexpression of p53 protein. Apoptosis levels were quite low in normal epithelial cells, moderate in low-grade PIN, and high in high-grade PIN and carcinomas. Levels of expression of proliferating cell nuclear antigen correlated with the degree of severity of the prostate lesions. Eighteen % of PIN lesions were found to already harbor Ha-ras mutations, whereas 33% of carcinomas showed various mutations in Ha-ras, Ki-ras, and/or p53. Mutations in Ha-ras may, therefore, be an early event in a significant portion of PIN lesions. Because high-grade PIN showed many characteristics similar to those observed in carcinomas and high-grade PIN was often found contiguous to carcinomas, we conclude that high-grade PIN is a precursor lesion of prostate carcinoma in this transgenic model. These transgenic mice will be useful to study mechanisms responsible for the progression of invasive carcinomas from PIN precursor lesions, as may occur during the development of prostate cancer in humans.

Links

J:72324 – Mouse Genome Informatics
8895741 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB/N-Tg(C3-1-TAg)cJeg Prostate gland - Anterior lobe lesion Prostate gland - Anterior lobe

0

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland - Dorsolateral lobe adenocarcinoma Prostate gland - Dorsolateral lobe

0 - 24

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland - Dorsolateral lobe prostatic intraepithelial neoplasia (PIN) Prostate gland - Dorsolateral lobe

0 - 100

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland - Ventral lobe adenocarcinoma Prostate gland - Ventral lobe

0 - 39

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland - Ventral lobe prostatic intraepithelial neoplasia (PIN) Prostate gland - Ventral lobe

0 - 100

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland adenocarcinoma Prostate gland

observed

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland prostatic intraepithelial neoplasia (PIN) Prostate gland

very high

FVB/N-Tg(C3-1-TAg)cJeg Seminal vesicle lesion Seminal vesicle

0