Blocking HER-2-Mediated Transformation with a Dominant Form of HER-3
Abstract
Amplification of the HER-2 gene often leads to breast cancer by causing cells to make abnormally high levels of the wild-type HER-2 protein. Evidence now shows that the interaction between HER-2 and HER-3 leads to the constitutive activation of HER-2/HER-3 heterodimers in breast cancer cells with HER-2 gene amplification, and HER-2/HER-3 potently activates multiple signal transduction pathways involved in mitogenesis. This indicates that inhibition of the interaction between HER-2 and HER-3 may be an especially effective and unique strategy for blocking the effects of HER-2 in human breast cancer cells. Therefore, we constructed retroviral expression vectors that code for a dominant negative form of HER-3 that can inactivate the function of HER-2/HER-3. Dominant negative HER-3 specifically inhibited proliferation induced by heregulin (the ligand for HER-2/HER-3) as well as the growth factor-independent (i.e. autonomous) proliferation and anchorage-independent growth of breast cancer cells with HER-2 gene amplification. We have used these dominant negative HER-3 vectors in experiments to determine the effectiveness of dominant negative HER-3 for blocking HER-2/HER-3 activation, signaling and growth in culture and in vivo for different breast cancer cell lines with HER-2 gene amplification.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA417299
Entities
People
- Tracy G. Ram
Organizations
- Washington State University