Role of Fibroblast Growth Factor Binding Protein-1 in Mammary Development and Tumorigenesis
Abstract
Fibroblast growth factors (FGFs) are vital modulators of development as well as angiogenesis. FGFs play a large role in vascular formation, body axis patterning, cell migration and organ branching. The scientific community is still piecing together the role that distinct FGFs play due to the complexity of the FGF network, which involves 22 distinct members that signal through 4 receptors to activate 3 major signaling pathways. As an added layer of complexity, FGF binding proteins (FGFBPs) release and activate FGFs from the extracellular matrix. FGFs act as major angiogenic factors and have therefore been of interest for therapeutic targeting. Success may rely on further elucidation of the regulation involved. The redundancy of FGF has made current FGF targeted therapies only moderately effective. Overexpression of human FGFBP1 in a conditional mouse model leads to decreased tertiary mammary ductal branching caused by increased epithelial apoptosis. This phenotype is seen only in mature mice that have fully developed mammary glands as opposed to pubertal mice developing altered mammary glands. FGFs have been strongly implicated in both dorsal/ventral axis patterning as well as mammary gland branching. This work supports the hypothesis that overexpressing human FGFBP1 in a developed mammary gland results in altered mammary gland structure. Furthermore, expression of human FGFBP1 in mammary tumors results in increased tumor size possibly due to FGFBP acting in its role as an angiogenic switch.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2008
- Accession Number
- ADA529372
Entities
People
- Krissa Gibby
Organizations
- Georgetown University