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Accession Number:
AD1031106
Title:
Wnt Signaling in Prostate Cancer Bone Metastases
Corporate Author:
The Ohio State University Columbus United States
Report Date:
2016-11-01
Abstract:
Ace-1-Dkk-1, a canine prostate cancer overexpressing Dkk-1 was used in this study to investigate how enhanced WntJNK signaling could alter tumor growth, metastasis and the bone microenvironment. Evidence was found that Dkk-1 up-regulated the non-canonical WntJNK pathway resulting with downstream alterations in gene expression important for osteoblast stimulation, cell proliferation and epithelial-to-mesenchymal transformation of cancer cells. Inhibition of non-canonical WntJNK signaling using SP600125 JNK inhibitorsignificantly increased the mRNA expression of genes that induced bone formation as well as decreased osteoclastic bone lysis in vitro. Dkk-1 increased tumor volume in mice. When mice were injected subcutaneously with Ace-1-Dkk1, treatment with SP600125 significantly reduced tumor size and altered tumor cell morphology. However, treatment with SP600125 did not alter tumor size in mice that were injected intra-tibially with Ace-1-Dkk1. Inhibition of non-canonical WntJNK signaling using SP600125 resulted in decreased tumor volume but did not alter tumor size in the bone.
Descriptive Note:
Technical Report,01 Sep 2014,31 Aug 2016
Pages:
0238
Distribution Statement:
Approved For Public Release;
File Size:
4.73MB
