Manipulation of NF-KappaBetta Activity in the Macrophage Lineage as a Novel Therapeutic Approach
Abstract
Morphogenesis of the mammary gland is a highly complex process which when misregulated can result in tumorigenesis. It involves the interactions of multiple cell types in a highly regulated manner with complex signal transduction pathways coordinating the physiological processes. Interactions between epithelial and mesenchymal cells are known to be important. Recent studies highlight the importance of cell types, such as macrophages. The nuclear factorkappa B (NF-kB) family of transcription factors appears to be critical in regulating the dynamic changes during normal and neoplastic development. This proposal seeks to investigate the contribution of NF-kB signaling within macrophages in normal and neoplastic mammary development. Our data will provide insights into the importance of NF-kB signaling in macrophages for tumor development and progression and have the potential for identification of novel therapeutic strategies. During this period we continued to characterize macrophages with constitutive NF-kappaB activity and identified differences in proliferation rates, expression of downstream gene expression and effects mediated by altered macrophages on associated epithelial cells. In addition, we have obtained the 3rd novel transgenic necessary for an inducible system to make feasible manipulation of NF-kappaB activity in macrophages in vivo. We have generated the double transgenics necessary to test our new models and have preliminary data to suggest that altered NF-kappaB activity within macrophages has significant effects on mammary ductal development.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2007
- Accession Number
- ADA471493
Entities
People
- Fiona E. Yull
Organizations
- Vanderbilt University Medical Center