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. Zn particular, ErbB-2 dysfunciton 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. 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. Zn this project, a vertebrate neuregulin-1 with an EGF domain deletion (NRGAEGF) and a factor with the EFG domain from the inhibitor (NRG::Aos-EGF) were made. The activity of the factors was tested in transgenic mice by examining heart defects which are characteristic of neuregulin defects. No defects were observed. The results suggest the factors are unlikely to be useful in regulating NRG function in the breast.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA418926
Entities
People
- Amanda A. Simcox
Organizations
- Ohio State University