Prostate carcinogenesis is a multi-step process that results in the transformation of prostatic epithelial cells into invasive carcinoma with the ability to metastasize to distant sites. Along the continuum of prostatic cellular transformation, several phenotypes are observed, including benign hyperplasia, prostatic intraepithelial neoplasia (PIN), and invasive carcinoma. In recent years, numerous mouse models have been generated that recapitulate some of the salient features of prostate carcinogenesis that are found in human disease. These models are critical to our understanding of the molecular events that result in transformation and disease progression. In addition, mouse models can be used to identify molecular targets and test chemotherapeutic agents that may alter the course of the disease. The overall goal of this proposal is to utilize an established, well characterized mouse model of prostate cancer to further delineate molecular targets that may halt cancer progression and/or lead to regression of metastatic disease. In order to rapidly evaluate a variety of select target genes in the long-term, we will create a new transgenic mouse which will allow for efficient and specific gene transfer of imaging genes combined with small hairpin nuclear RNAs (shRNAs) that can cause knockdown of potential oncogenes. The development of this mouse will enable prostate cancer development, progression, and the effect of target gene knockdown via RNA interference with shRNAs to be monitored non-invasively in mice over time. This approach will facilitate high throughput analysis of genes that may turn out to be powerful therapeutic targets in the future.