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- W2061606882 abstract "The skeleton is the most common site of metastasis in human prostate cancer (PCa). Through over-expression of the Wnt inhibitor Dickkopf-1 (DKK-1), we previously demonstrated that Wnts contribute to the osteoblastic component of PCa skeletal metastases. Herein, we demonstrate that knock-down of DKK-1 using shRNA in osteolytic PC-3 PCa cells delayed the development of both soft tissue and osseous lesions compared to DKK-1+ control shRNA cells. Similarly, systemic treatment with a DKK-1 neutralizing antibody decreased overall tumor burden following intracardiac injection of PC-3 cells 8.3-fold compared to IgG-treated control mice (p<0.028) demonstrating that DKK-1 facilitates tumor growth. DKK-1 shRNA transfected cells were found to have increased expression of the cyclin dependent kinase inhibitor p21CIP1/WAF1 (CDKN1A) and a 32% increase in G1 arrest compared to DKK-1+ shcontrol transfected cells. Simultaneous knock-down of p21 accelerated tumor growth of DKK-1 shRNA transfected cells in vivo suggesting that DKK-1 knock-down led to p21-mediated suppression of cell cycle and tumor growth. Taken together, the data support the hypothesis that DKK-1 expression in PCa cells facilitates tumor growth by blocking Wnt-mediated suppression of cell cycle through p21." @default.
- W2061606882 created "2016-06-24" @default.
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- W2061606882 date "2011-01-01" @default.
- W2061606882 modified "2023-10-09" @default.
- W2061606882 title "Peripheral cannabinoid type 2 receptor regulates osteoclast formation, MDA-MB-231 breast cancer cell migration and bone marrow/tumour cell interaction via PI3 kinase/AKT and P38 pathways" @default.
- W2061606882 doi "https://doi.org/10.1016/j.bone.2010.10.124" @default.
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