Fibroblast growth factors in development and cancer: insights from the mammary and prostate glands

Abstract

The fibroblast growth factor (FGF) family is comprised of 22 ligands that bind and activate several FGF receptor (FGFR) isoforms. Critical roles for FGFs and FGFRs have been well-established during embryonic development. For example, the FGF10/FGFR2IIIb axis has been linked to embryonic development of both the mammary and prostate glands, which are the subject of this review. Furthermore, recent studies using novel mouse models have suggested that this pathway also participates in postnatal development in the mammary and prostate glands. These studies have provided novel insights into the mechanisms by which FGFs and FGFRs promote ductal outgrowth and branching morphogenesis. In addition to the established roles of FGFs in development, aberrant activation of the FGF pathway has been linked to tumor progression in both breast and prostate cancer. Recent studies have linked FGFR1 expression and single nucleotide polymorphisms in FGFR2 to breast cancer. Furthermore, novel pre-clinical models have demonstrated the ability of FGFRs to promote numerous aspects of breast and prostate cancer. Understanding the roles of FGFs in development will provide insights into the mechanisms by which deregulation of the FGF pathway leads to tumorigenesis, ultimately leading to the development of novel therapeutic strategies designed to target this pathway in cancer patients.