WNT-Signals and the Regulation of Normal and Cancerous Growth in the Mammary Gland
Final rept. 15 Sep 1994-14 Sep 1999
HARVARD UNIV CAMBRIDGE MA
Pagination or Media Count:
Wnt genes encode a large family of secreted signaling molecules related to the Drosophila pattern regulating gene wingless. Several members of the Wnt family have been implicated in mammary tumorigenesis suggesting that Wnt-activated pathways are a normal component of mammary gland development. Consistent with this hypothesis we have demonstrated that seven Wnt genes are expressed in the mammary gland at different stages of development. We have started to dissect their activities genetically. One of these, Wnt5b, was mutated by gene targeting. However, Wnt5b mutant females exhibit normal mammary gland structure and function. A second member, Wnt4 was investigated by mammary epithelial grafting and found to play a role in ductal branching with a phenotype similar to progesterone receptor mutants. Further analysis supports a linkage between these pathways. We also determined that Lmxlb, a target of Wnt-signaling in the limb, is required at embryonic stages for development of the mammary gland. Finally, we have developed strains of mice which will allow mammary epithelial specific CRE-mediated modification of gene activity which should be a useful resource for the scientific community.
- Anatomy and Physiology
- Medicine and Medical Research