A secreted carrier protein has been described which is able to bind to FGF-l and FGF- 2 in a non-covalent, reversible manner. EGF-2 bound to this protein was not subject to degradation and retained its mitogenic activity. This FGF-binding protein (FGF-BP) has been studied extensively by our laboratory. FGF-BP is highly expressed in squamous cell carcinomas (SCC) and EGF is able to increase the expression of FGF-BP in SCC derived cell lines through PKC, MSK/ERK, and p38 MAPK signaling. We have found FGF-BP mRNA to be expressed in two breast cancer cell lines (MDA-MB-468, MCF-7/ADR), by Northern Analysis/Pibonuclease Protection. EGF treatment of MDA-MB-468 cells resulted in an increase in FGF-BP mRNA expression in a time-dependent manner. EGF signaling occurs primarily through the PKC, and p38 MAPK pathways. Finally, EGF induction of the EGF-EP promoter is mediated through CCAAT/enhancer binding protein and AP-l transcription factor binding sites on the promoter.