Study the Pathogenic Role of ErbB-3, ErbB-4 and their Ligand Heregulin in Human Breast Cancer Cells.
Abstract
The EGF-like receptor tyrosme kinase farnily is frequently overexpressed in a variety of human carcinomas, including breast cancer. To assist in characterizing the role of ErbB-4 in breast cancer, we generated three specific hamrnerhead ribozymes targeted to the ErbBA mRNA. These ribozymes, Rz6, Rz21, and Rz29, efficiently catalyzed the specific cleavage of ErbBA message in a cell-free system. We demonstrated that the heregulin induced mitogenic effect was abolished in ribozyme Rz29 and Rz6 transfected 32D/ErbBA cell. In addition, we provide the first evidence that different threshold levels of ErbBA expression and activation correlate with different responses to llRG stimulation. Furthermore, expression of the ftmctional ErbBA ribozyme in T47D human breast carcinoma cells lead to a down regulation of endogenous ErbBA expression and a reduction of anchorage-independent colony formation. This preliminary result suggests that ErbBA plays a role in human breast cancer. We wlll expend our studies on investigation of the biological effect on down-regulation of ErbB-3 receptor expression by a ribozyme targeting ErbB-3 in breast cancer cells in vitro and in vivo. These studies will support the potential use of ribozymes as therapeutic agents for human breast cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1997
- Accession Number
- ADA332797
Entities
People
- Careen Tang
Organizations
- Georgetown University