Prostate cancer in a transgenic mouse.

TLDR

Progress toward understanding prostate cancer biology has been slow because few animal models exist to study this uniquely human disease. The authors established breeding lines of transgenic mice expressing SV40 large T antigen under a prostate‑specific promoter to provide a reproducible model for studying the molecular basis of prostate cancer transformation and progression to metastasis. They generated multiple transgenic lines by driving SV40 large T antigen expression with the rat probasin promoter in the prostate. High transgene expression led to progressive prostatic lesions that histologically mirror human cancer, with tumors detectable by 10 weeks, ranging from intraepithelial hyperplasia to multinodular malignancy, and exhibiting elevated nuclear p53, altered androgen‑receptor heterogeneity, and restricted dorsolateral secretory protein expression.

Abstract

Progress toward understanding the biology of prostate cancer has been slow due to the few animal research models available to study the spectrum of this uniquely human disease. To develop an animal model for prostate cancer, several lines of transgenic mice were generated by using the prostate-specific rat probasin promoter to derive expression of the simian virus 40 large tumor antigen-coding region. Mice expressing high levels of the transgene display progressive forms of prostatic disease that histologically resemble human prostate cancer, ranging from mild intraepithelial hyperplasia to large multinodular malignant neoplasia. Prostate tumors have been detected specifically in the prostate as early as 10 weeks of age. Immunohistochemical analysis of tumor tissue has demonstrated that dorsolateral prostate-specific secretory proteins were confined to well-differentiated ductal epithelial cells adjacent to, or within, the poorly differentiated tumor mass. Prostate tumors in the mice also display elevated levels of nuclear p53 and a decreased heterogeneous pattern of androgen-receptor expression, as observed in advanced human prostate cancer. The establishment of breeding lines of transgenic mice that reproducibly develop prostate cancer provides an animal model system to study the molecular basis of transformation of normal prostatic cells and the factors influencing the progression to metastatic prostate cancer.