Actions and Substrates for the HER4 Tyrosine Kinase in Breast Cancer
Abstract
The EGF receptor family consists of four members (EGFR and HER 2, 3 and 4). One, HER2, is overexpressed in 20-25% of human breast cancers through gene amplification while another, the EGF receptor, is thought to be overexpressed or activated in poor prognosis breast cancers. Our objective was to determine whether the most recently discovered member, HER4, triggers a distinct, anti-proliferative and differentiation signal in breast cell lines and could therefore be a marker breast cancer with a better prognosis. After cloning the HER4 cDNA and constructing various chimeric and mutant receptors, we created novel breast cell lines expressing a variety of molecular constructs. These were used to conclusively demonstrate that HER4 activation stimulated anti-proliferative and differentiation responses in breast cell lines, even in the absence of HER2 signaling. Thus HER4 is both necessary and sufficient to slow the growth of breast cancer cell lines. Studies in our extension year will define gene expression by microarray technology, delineating HER4 versus combined HER2 HER4 signals.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA384377
Entities
People
- H. S. Earp
Organizations
- University of North Carolina at Chapel Hill