WNT Proteins in Mammary Epithelial Cell Transformation.
Annual rept. 1 Jun 95-31 May 96,
COLUMBIA UNIV NEW YORK
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We have assessed the ability of Wnt-l, Wnt-2, Wnt-3, Wnt-3A, Wnt-4, Wnt-5A, Wnt-5B, Wnt- 6, Wnt-7A, and Wnt-7B to transform mammary epithelial cells. The transforming potential of Wnt proteins was tested in C57MG mammary epithelial cells. Paracrine transforming capability of Wnt genes was tested by co-cultivating mammary epithelial cells with Wnt-expressing Rat fibroblasts. Direct and paracrine transforming assays indicates that Wnt-l, 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. Wnt gene family members thus differ in their potential to morphologically transform mammary epithelial cells, suggesting several distinct receptors or quantitative differences in the signals different Wnt proteins provide. By generating chimeric Wnt proteins we have defined two regions of Wnt- 1 that are critical for transformation potential. We have identified a co-factor activity produced by mammary epithelial cells that may be required for full Wnt activity. Finally, using adenovirus vectors we have documented that Wnt proteins may be involved in inducing apoptosis in some cellular systems.
- Medicine and Medical Research