Role of the Mouse Pygopus 2 Gene and Wnt Signaling in Normal and Malignant Development of Mammary Glands and Hair Follicles

摘要

The development of mammary gland is governed by multiple genetic pathways although how these pathways are regulated and how they interact with each other is not yet fully understood. Previous studies have implicated the involvement of the canonical Wnt signaling pathway which includes several key components that act together to activate other genes that are directly involved in controlling cell division or differentiation in both normal and abnormal mammary gland development. The timing and overall activity of the pathway is key as its disruption leads to aberrant mammary development and its over stimulation leads to breast cancer. We proposed genetic experiments to examine the role of a novel component of the Wnt pathway in mammary gland development and tumorigenesis. Specifically we proposed to target genetic manipulations to a subset of the mammary epithelial cells that have stem cell characteristics. The mutant mice generated in this study should provide novel animal models to study the ontogeny and progression of mammary tumors. Furthermore results from our studies should provide some insight into the role of epithelial stem cells in normal and diseased development. Finally our studies might implicate possible drug target for treating breast cancer in the future.