Accession Number : AD1031106


Title :   Wnt Signaling in Prostate Cancer Bone Metastases


Descriptive Note : Technical Report,01 Sep 2014,31 Aug 2016


Corporate Author : The Ohio State University Columbus United States


Personal Author(s) : Supsavhad,Wachiraphan


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/1031106.pdf


Report Date : 01 Nov 2016


Pagination or Media Count : 238


Abstract : Ace-1-Dkk-1, a canine prostate cancer overexpressing Dkk-1 was used in this study to investigate how enhanced Wnt/JNK signaling could alter tumor growth, metastasis and the bone microenvironment. Evidence was found that Dkk-1 up-regulated the non-canonical Wnt/JNK 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 Wnt/JNK signaling using SP600125 (JNK inhibitor)significantly 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 Wnt/JNK signaling using SP600125 resulted in decreased tumor volume but did not alter tumor size in the bone.


Descriptors :   prostate cancer , metastasis , Bones , neoplasms


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE