Notch and VEGF Interactions in Breast Cancer
Abstract
The proposal objective is to define the interaction between Notch and VEGFR-3 in breast cancer. Thus, we proposed to investigate this relationship in four different settings: primary endothelial cell cultures, mouse embryos, human breast tumors, and mouse mammary tumor xenografts. In the first year, we have completed the characterization of Notch regulation of VEGFR-3 in primary endothelial cells and begun the evaluation of Notch and VEGFR-3 expression in mouse embryos and human breast cancers. Our preliminary data demonstrated that expression of an activated form of Notch4 increased VEGFR-3 transcripts in three different human primary endothelial cells. Using cell surface biotinylation and immunoblotting, we have found that activated forms of both Notch I and Notch4 induced VEGFR-3 protein in the endothelial cell lines. This induction of VEGFR-3 in vitro was also observed in embryos in which Notch4 was activated within the endothelium. In contrast, the expression of VEGF-C, a ligand for VEGFR-3, was unaffected by Notch signal activation; while, VEGF-D was not expressed, nor induced by Notch in the endothelial cell lines examined. Initial experiments indicate that Notch 1, Notch4 and VEGFR-3 are expressed within the vasculature of normal breast and ductal carcinomas, as well as the ductal epithelial cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA425129
Entities
People
- Carrie J. Shawber
Organizations
- Columbia University