WNT Proteins in Mammary Epithelial Cell Transformation.
Annual rept. 1 Jun 96-31 May 97,
COLUMBIA UNIV NEW YORK
Pagination or Media Count:
We have assessed the ability of Wnt-1, Wnt-2, Wnt-3, Wnt-3A, Wnt-4, Wnt-5A, Wnt-5B, Wnt-6, Wnt-7A, and Wnt-7B to transform mammary epithelial cells and found that Wnt-1, Wnt-2, Wnt-3 and Wnt-3A proteins transform mammary epithelial cells Wnt-7A and Wnt-7B proteins partially transform and Wnt-4, Wnt-5A, Wnt-5B, and Wnt-6 proteins does not affect mammary epithelial cells. Transformation correlated with Wnt-mediated increases in the cytosolic pool of beta-catenin. By generating chimeric Wnt proteins and Wnt-1 deletions we have defined regions of Wnt-1 that are critical for transformation potential, signal transduction and frzb association. We have demonstrated that a secreted protein, frzb, blocks Wnt signaling and that a cytosolic protein, fused, is a negative regulator of Wnt signaling in mammalian cells. Wnt-1 acts as a mitogen in cultured Rat-1 fibroblasts, allowing growth of cells in serum-free medium. Using the TAC-2 mammary epithelial cell line, we found that Wnt-1 induces branching morphogenesis of mammary epithelial cells and can act as a morphogen in this capacity.
- Anatomy and Physiology