Killing Breast Cancer Cells With a VEGF-Triggered Cell Death Receptor
Abstract
Many breast cancers overexpress the tumor angiogenesis factor VEGF (vascular endothelial growth factor). Consequently numerous VEGF inhibitors are being studied. Some such as bevacizumab extend progression-free survival but have not yet been shown to extend overall survival in breast cancer patients. We are pursuing a totally different approach to targeting VEGF: rather than inhibit VEGF our goal is to convert VEGF to act as a cell death factor. Toward this aim we created a chimeric receptor (R2Fas) composed of domains from VEGF receptor 2 fused to the intracellular domain of the Fas cell death receptor. As controls we generated two inactive versions of R2Fas with mutations in the VEGF receptor 2 domain or the Fas domain. Replication-defective adenoviruses expressing each of the receptors were generated and used to direct expression of the receptors in human breast cancer cell lines. We found that expression of the R2Fas chimeric receptor but not the inactive control receptors could induce apoptosis in several human breast cancer cell lines in vitro. These studies suggest that a receptor such as R2Fas which converts VEGF to act as a cell death factor could yield a new and more aggressive approach to targeting overexpressed VEGF in breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2006
- Accession Number
- ADA478905
Entities
People
- Timothy Quinn
Organizations
- University of California, San Francisco