A Modulator of FGF's in Breast Cancer
Abstract
The growth of new blood vessels, or angiogenesis, is an important part of breast cancer biology. We have found that a secreted binding protein for fibroblast growth factors (FGF-BP) is expressed in many breast cancer cell lines and primary breast tumor samples. In addition, FGF-BP is expressed in squamous cell carcinoma and colon cancer and modulation of FGF-BP expression in these tumor types has a significant effect on tumor growth and angiogenesis. In order to better understand the regulation of FGF-BP and how its aberrant expression might lead to activation of angiogenic pathways, I isolated the human FGF-BP promoter and determined which functional promoter elements were necessary for its expression. In particular, I found that the FGF-BP gene is transcriptionally up-regulated by the phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate) which - activates the protein kinase C (PKC) pathway. The positive regulatory elements which mediate FGF-BP induction by TPA include a juxtaposed Ets/AP-1 site as well as a C/EBP site. Furthermore, the presence of a distinct repressor element was detected which normally limits the response of the promoter to TPA. Additionally, I found that the FGF-BP is induced in the presence of EGF (epidermal growth factor), which is known to play an important role in the pathogenesis of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1998
- Accession Number
- ADA360424
Entities
People
- Violaine K. Harris
Organizations
- Georgetown University