Award Number : W 81 XWH - 08 - 1 - 0030 TITLE : Regulation of Prostate Cancer Bone Metastasis by DKK 1 PRINCIPAL INVESTIGATOR :

✓ Approved for public release; distribution unlimited Distribution limited to U.S. Government agencies only; report contains proprietary information The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. Osteoblastic bone metastasis is a common complication of advanced prostate cancer, resulting in pain and pathologic fracture. Dickkopf homolog 1 (DKK1) is a secreted inhibitor of osteoblast Wnt signaling pathway and hypothesized to be a central regulator of prostate cancer osteoblastic bone metastasis. The purpose of this proposal is to examine mechanisms of DKK1 regulation by prostate cancer cells and determine whether DKK1 overexpression in bone blocks the formation of osteoblastic bone lesions in animal models of bone metastasis. We have now shown that human prostate cancer cell lines that produce osteolytic, but not osteoblastic, bone lesions in animal models of bone metastasis express significant amounts of DKK1 and this expression is correlated with the absence of DNA methylation at the DKK1 promoter CpG island. Our preliminary data points to a central role of DKK1 in prostate cancer bone metastasis and expect this work to translate into the development of novel therapeutic targets to treat this malignancy complication.