Tyrosine kinase signalling in breast cancer - Fibroblast growth factors and their receptors

The fibroblast growth factors [Fgfs (murine), FGFs (human)] constitute a la rge family of ligands that signal through a class of cell-surface tyrosine kinase receptors. Fgf signalling has been associated in vitro with cellular differentiation as well as mitogenic and motogenic responses. In vivo, Fgf s are critical for animal development, and some have potent angiogenic prop erties. Several Fgfs have been identified as oncogenes in murine mammary ca ncer, where their deregulation is associated with proviral insertions of th e mouse mammary tumour virus (MMTV). Thus, in some mammary tumours of MMTV- infected mouse strains, integration of viral genomic DNA into the somatic D NA of mammary epithelial cells was found to have caused the inappropriate e xpression of members of this family of growth factors. Although examination of human breast cancers has shown an altered expression of FGFs or of thei r receptors in some tumours, their role in the causation of breast disease is unclear and remains controversial.