Approximately 25% of men with prostate cancer develop tumor at locations remote from the prostate gland. Prostate cancer mortality is strongly correlated with the development of tumor metastatic disease. Clinical findings indicate existence of significant growth control or metastasis inhibition mechanisms at secondary sites of metastases. Therefore, it is critical to understand the cellular and molecular events that predispose tumor cells to undergo metastasis. In this research proposal, we plan to use an experimental model of metastatic prostate cancer developed in mice. This model allows us to study the tendency of prostate cancer cells to undergo metastasis. We predict that the tendency for metastasis can be explained by a small subpopulation of cells that have acquired a new genetic defect. We have access to experimental mouse prostate tumor cells that either undergo metastasis or remain localized. We plan to compare the expression patterns of genes in metastatic cells with those of non-metastatic cells. We will then correlate these patterns of gene expression with genomic defects in the cells. The ultimate goal of this project is to identify a subset of genes that may prevent metastasis under normal conditions, but promote metastasis when certain genetic defects occur. Once candidate metastasis-suppressor genes have been identified, their ability to suppress metastasis in a biological assay will be confirmed. Results from these experiments will provide new information on genes required for the metastasis of prostate cancer. These findings will improve diagnostic and prognostic abilities of physicians caring for these patients as well as leading to new therapeutic targets to prevent metastatic spread of prostate cancer. The proposed experiments will provide the candidate with new training in cancer biology, and further maturation in bioinformatics. It is expected that his accomplishments during this K01 award period will help the candidate become an independent research in the future.
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