Activation of Alternative Wnt Signaling Pathways in Human Mammary Gland and breast Cancer Cells
Abstract
Wnts are lipid-bound glycoproteins that can regulate diverse biological processes in many different cell systems. I have found that Wnt-5a, a member of the Wnt family unable to stabilize cytosolic Beta-catenin in endothelial cells and, in consequence, a noncanonical Wnt, is endogenously expressed in human primary endothelial cells as well as closely related member 5b. Overexpression of Wnt-5a in human endothelial cells was able to induce cell proliferation and enhance survival under serum-deprived conditions. Regulation of in vitro cell proliferation was blocked by addition of purified Frizzled-4 extracelullar domain, showing evidence that this Frizzled, a receptor know to trigger canonical Wnt signaling response, can also mediate alternative Wnt signaling. Cells ectopically overexpressing Wnt-5a were also able to show improved network formation capabilities when cultured on top of extracellular matrix proteins. After a DNA array analysis screening a large number of target genes, we confirmed that in human microvascular cells, alternative Wnt signaling can upregulate expression of matrix metalloproteinase- 1 (MMP- 1), an interstitial collagenase, both at message and protein expression level.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2005
- Accession Number
- ADA441325
Entities
Organizations
- Columbia University