FGF receptor signaling & functions in the mammary gland
The FGF receptor (FGFR) signaling pathways have an important role in the development and differentiation of the human mammary gland . The FGFRs are cell membrane bound receptor tyrosine kinases that are activated by binding FGF ligands. The FGFR family includes seven tyrosine kinase members (FGFR1b and c, FGFR2b and c, FGFR3b and c, and FGFR4) that bind FGFs selectively with different binding specificities leading to distinct biological actions . In addition, there is FGFR5, which binds FGFs, but which lacks the intracellular tyrosine kinase domain. The FGF family comprises 22 members and 18 of them function as ligands for FGFRs. Interaction of FGFs with FGFR1–4 leads to the activation of intracellular signaling pathways, such as ERK–MAPK, PI3K and PLC pathways. They lead to multiple cellular responses including stimulation of cell proliferation, cell survival, tissue repair processes and angiogenesis. FGFR5 is not able to activate intracellular signaling and its putative functions are presently unknown. Although FGFR1–4 signal via the same pathways their regulation and biological actions are different , and highly context specific [2,4]. This is presumably caused by the cell- and tissue-specific expression patterns of FGFs and FGFRs. In normal glandular tissues, such as the mammary gland, FGFs typically signal directionally from the epithelium to stroma and vice versa. By this complex network, FGF/FGFR signaling plays a major role in maintaining and regulating the epithelial stromal interactions and homeostasis within the tissue [2,4].