The goal is to establish a well characterized in vivo transgenic animal model and utilize this model(s) to elucidate the key events in carcinogenesis and prostate tumor progression. Transgenes under the control of a large fragment of the probasin (PB) promoter delivers high levels of gene expression that is regulated both hormonally and developmentally in prostatic epithelial cells in transgenic mice. Using this large PB promoter linked to the SV40 large T antigen, seven transgenic mouse lines have been established that develop prostatic disease. The initial studies reveal that preneoplastic lesions similar to human prostatic intraepithelial neoplasia develop in the mouse prostate and progress onto an androgen dependent cancer of the prostate. The goals of this research are to complete the characterization of the new transgenic animal models for CaP, to identify changes in gene expression in the sequential stages of tumor progression by using differential display, and to select and characterize the key molecular differences during tumor progression. These new transgenic CaP models will facilitate the elucidation of molecular events from the early stages of prostatic carcinogenesis to the late stages of tumor progression.
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