PROSTATE-CANCER IN A TRANSGENIC MOUSE

Progress toward understanding the biology of prostate cancer has been slow due to the few animal research models available to study the spec trum of this uniquely human disease. To develop an animal model for pr ostate cancer, several lines of transgenic mice were generated by usin g the prostate-specific rat probasin promoter to drive expression of t he simian virus 40 large tumor antigen-coding region. Mice expressing high levels of the transgene display progressive forms of prostatic di sease that histologically resemble human prostate cancer, ranging from mild intraepithelial hyperplasia to large multinodular malignant neop lasia. Prostate tumors have been detected specifically in the prostate as early as 10 weeks of age. Immunohistochemical analysis of tumor ti ssue has demonstrated that dorsolateral prostate-specific secretory pr oteins were confined to well-differentiated ductal epithelial cells ad jacent to, or within, the poorly differentiated tumor mass. Prostate t umors in the mice also display elevated levels of nuclear p53 and a de creased heterogeneous pattern of androgen-receptor expression, as obse rved in advanced human prostate cancer. The establishment of breeding lines of transgenic mice that reproducibly develop prostate cancer pro vides an animal model system to study the molecular basis of transform ation of normal prostatic cells and the factors influencing the progre ssion to metastatic prostate cancer.