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Manipulation of NF-KappaB Activity in the Macrophage Lineage as a Novel Therapeutic Approach
Annual rept. 19 Apr 2005-18 Apr 2006
VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
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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. However, recent studies are beginning to highlight the importance of other cell types, such as macrophages. One of the signaling molecules that appears to be critical in regulating the dynamic changes during normal and neoplastic development is the nuclear factor-kappa B NF-kB family of transcription factors. NF- kB can regulate many genes that are expressed by macrophages that are important for proliferation and apoptosis of cells, as well as remodeling and angiogenesis. This proposal seeks to investigate the contribution of NF-kB signaling within macrophages in defining the macrophage s role in normal and neoplastic mammary development. The proposed studies will provide information regarding the signaling pathways involved in normal mammary development. They will also provide insights into the importance of NF-k signaling in macrophages for tumor development and progression and will have the potential for identification of novel therapeutic strategies. At this point we have generated a novel transgenic reporter that allows us to investigate patterns of NF-kappaB activity during mammary development.
APPROVED FOR PUBLIC RELEASE