Regulation of Neu Signaling in Breast Cancer
Abstract
ERBB-2/neu amplification and overexpression is the most common genetic alteration in breast cancer. As a growth factor receptor and member of the EGFR family, erbB-2 signaling is dependent upon target tissue expression of erbB-2 regulating growth factors and other EGFR family members. To determine the role erbB-2 plays in malignant mammary gland development I examined expression of each EGFR family member and their ligands during normal development of the mouse mammary gland. I found that each receptor is expressed throughout mammary gland development. In contrast, mammary gland expression of the erbB-2 agonists AR and HRG is developmentally regulated - AR being expressed in virgin mice and HRG expressed during pregnancy. This result suggested that erbB-2 agonists may drive mammary gland development. To test this hypothesis I implanted pellets containing HRG within mammary glands of virgin mice. I found that HRG could induce differentiation of mammary epithelium in this system. I predict that erbB-2 expressing breast tumor cells may be induced to differentiate by amplifying the HRG signaling pathway in these cells. I am currently designing experiments in an attempt to decipher the HRG signaling pathway.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1997
- Accession Number
- ADA347728
Entities
People
- David F. Stern
- Frank Jones
Organizations
- Yale University