Development of an erbB Antagonist
Abstract
Receptor tyrosine kinases of the erbB family play pivotal roles in growth and differentiation and aberrant activation of these receptors is associated with human cancers. In particular, ErbB-2 dysfunction has been linked to about 30% of breast cancers with poor prognosis. Correspondingly, great efforts are being made to develop therapies that target ErbB pathways. ErbB-2 is activated by the neuregulins in heterodimers with the neuregulin receptors ErbB-3 and ErbB-4. An antagonistic neuregulin that down regulates ErbB signaling could function as an anti-tumor agent with significant clinical potential. The purpose here is to develop such a factor. In previous work, the Drosophila system was used to demonstrate that an antagonistic neuregulin-like factor could be made by deleting the EGF domain or by insertion of the EGF domain from a natural inhibitor. In this project, a vertebrate neuregulin with an EGF domain deletion and a factor with the EGF domain from the inhibitor were made and appear to have inhibitory activity in vitro. The activity of the factors is now being tested against human breast-cancer cell lines. Corresponding constructs have been made to generate transgenic mice and these will provide an in vivo test of the factors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA385780
Entities
People
- Amanda Simcox
Organizations
- Ohio State University