Growth Factor Regulation of an Angiogenic Factor, the Fibroblast Growth Factor-Binding Protein (FGF-BP), in Breast Cancer
Abstract
A secreted carrier protein has been described which is able co bind to FGF-l and FGF-2 in a non-covalent, reversible manner. FGF-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, MEK/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/Ribonuclease Protection. EGF treatment of MDA-MB-468 cells resulted in an increase in FGF-EP mRNA expression in a time-dependent manner. EGF signaling occurs primarily through the PKC, and p38 MAPK pathways, while EGF induction of the FGF-BF promoter is mediated through CCAAT/enhancer binding protein (C/EBP) and AP-l transcription factor binding sites on the promoter. Finally, overexpression of C/EBPbeta-LAP upregulates FGF-BP promoter activity 80-fold and is reversed with coexpression of C/EBPbeta-LAP, which is mediated primarily through the FGF-BP promoter C/EBP site.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA410065
Entities
People
- Benjamin L. Kagan
Organizations
- Georgetown University