Dickkopf-related protein 3 promotes pathogenic stromal remodeling in benign prostatic hyperplasia and prostate cancer.
Bottom Line: Knockdown of DKK3 significantly attenuated PrSC proliferation as well as fibroblast-to-myofibroblast differentiation and increased the expression of the vessel stabilizing factor angiopoietin-1.DKK3 knockdown did not affect subcellular localization or levels of β-catenin but attenuated AKT phosphorylation in PrSCs.Consistently the PI3K/AKT inhibitor LY294002 mimicked the effects of DKK3 knockdown.
Affiliation: Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria. firstname.lastname@example.orgShow MeSH
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Mentions: The specific PI3K inhibitor LY294002 was used to investigate whether attenuation of AKT phosphorylation in DKK3-shRNA PrSCs is responsible for the modulatory effects of DKK3 knockdown on angiogenesis and fibroblast-to-myofibroblast differentiation marker expression. PI3K inhibition significantly attenuated cellular proliferation in a dose-dependent manner (Fig. 5A; 0 vs. 10 µM: P = 0.010; 10 vs. 20 µM: P = 0.044). Moreover, similar to DKK3-shRNA, the reduction in proliferation upon PI3K inhibition was associated with elevated CDKN1B/p27KIP1 mRNA and protein levels and reduced p21CIP1 protein levels while CDKN1A mRNA levels were increased (Fig. 5B and Supplemental Fig. 1). Dkk-3 levels were unaffected by LY294002 (Fig. 5B).
Affiliation: Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria. email@example.com