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Norman M Greenberg

Jeffrey M Rosen

Robert J Matusik

Several lines of transgenic mice have been generated using the prostate-specific rat probasin (PB) gene promoter to drive expression of the SV40 T antigen (Tag) coding region. Mice expressing high levels of the transgene specifically display progressive forms of prostatic cancer that histologically resemble human prostate cancer ranging from mild prostatic intraepithelial neoplasia (PIN) to large multinodular malignant adenocarcinoma with metastasis. Adenocarcinomas of the prostate have been detected as early as 10 weeks of age with extracapsular extension (ECE) and seminal vesicle invasion (SVI). 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 heterogenous pattern of androgen receptor (AR) expression as observed in advanced human prostate cancer. The establishment of breeding lines of transgenic mice that reproducibly develop prostate cancer with metastasis provides a unique animal model system to study the molecular basis of transformation of normal prostatic cells and the factors influencing the progression to metastatic prostate cancer.

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Houston, TX, United States of America

Norman M Greenberg