Wnt Signaling in Prostate Cancer Bone Metastases
Abstract
Ace-1-Dkk-1, a canine prostate cancer overexpressing Dkk-1 is used in this study to investigate how enhanced Wnt/JNK signaling could alter metastasis and the bone microenvironment. Evidence was found that Dkk-1 up-regulated the non-canonical Wnt/JNK pathway resulting in downstream alterations in gene expression important in osteoblast stimulation, cell proliferation and epithelial to mesenchymal transformation of tumor cells. Inhibiting non-canonical Wnt/JNK signaling using SP600125, a JNK inhibitor, did not cause the canonical Wnt signaling to resume in Ace-1-Dkk1 cells. However, SP600125 significantly increased the mRNA expression of genes that induce osteoblast differentiation as well as decreased osteolytic genes (decreased RANKL:OPG ratio) in both Ace-1-Dkk1 and Ace-1-Vector cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2015
- Accession Number
- ADA623452
Entities
People
- Wachiraphan Supsavhad
Organizations
- Ohio State University