Regulation of the Angiogenic Factor FGF Binding Protein (FGF-BP) by the APC/Beta-Catenin Signaling Pathway in the Progression of Breast Cancer

摘要

Fibroblast growth factor binding protein (FGF-BP) releases immobilized FGFs from the extracellular matrix and can function as an angiogenic switch molecule in cancer. We have determined that FGF-BP is upregulated in a portion of breast cancers and this upregulation is correlated with increased expression of beta-catenin. In this grant we hypothesized that beta-catenin can initiate angiogenesis in mammary carcinoma through FGF-BP. The aims were 1) to study the expression of FGF-BP in mammary tumorigenesis progression of the APC/+ mouse and 2) to determine the mechanism of regulation of FGF-BP b the APC/beta- catenin signaling pathway in breast cancer. To date, we have shown a positive correlation of upregulation of beta-catenin expression and FGF-BP in breast and other tumors in the APC/+ mice. We have also shown that beta-catenin can directly induce FGF-BP gene expression through a transcriptional mechanism and that a TCF site in the FGF-BP promoter is responsible for a major portion of this effect. To further study the nature and specificity of this interaction, we performed gel shift assays and determined that the TCF site at -1030 in the FGF- BP promoter is necessary for this interaction.