HER2/neu Antisense Therapeutics in Human Breast Cancer
Abstract
In order to define mechanisms by which HER2/neu overexpression drives breast cancer cell growth and chemoresistance, antisense oligodeoxynucleotides (ODNs) have been used to down-regulate HER2/neu expression in human breast cancer cells. Such antisense ODNs suppress HER2/neu mRNA and protein expression in a dose-dependent, sequence-specific manner. Antisense ODN-mediated down-regulation of HER2/neu expression in HER2/neu- overexpressing breast cancer cells inhibits cell cycle progression in GO/GI and results in apoptotic cell death. In tissue culture studies, combined treatment of HER2/neu overexpressing breast cancer cells with HER2/neu antisense ODNs and conventional chemotherapeutic agents results in synergistic inhibition of cell growth and activation of apoptosis. These studies have been extended to demonstrate synergistic antitumor effects following systemic treatment with HER2/neu antisense ODNs and chemotherapeutic agents in breast cancer xenografts in nude mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA470204
Entities
People
- Jeffrey A. Drebin
Organizations
- University of Washington