Regulation of Prostate Cancer Bone Metastasis by DKK1
Revised final rept. 1 Apr 2008-28 Aug 2012
ALABAMA UNIV IN BIRMINGHAM
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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.
- Medicine and Medical Research