Role of IGFBP-3/IGFBP-3 Receptor Interaction in Normal and Malignant Mammary Growth: A Potential Diagnostic Parameter and New Strategy for Endocrine Therapy
Abstract
The proposal of my grant is to investigate the biological significance and mechanism of insulin-like growth factor binding protein-3 (IGFBP-3) as well as identification and characterization of the IGFBP-3 receptor in human breast cancer cells. As a third year task, we have successfully characterized binding specificity of the IGFBP-3 receptor to IGFBP-3. It revealed that only IGFBP-3 and its fragment (aa88-148) bind the IGFBP-3 receptor with high affinity, whereas IGFBPs, -2,4-, -5 and did not interact with the IGFBP-3 receptor, demonstrating specificity of the IGFBP-3 receptor. We have also identified the IGFBP-3/IGFBP-3 receptor-mediated signal transduction pathway in human breast cancer cells. Current studies demonstrated that the IGFBP-3/IGFBP-3 receptor axis causes cell cycle arrest in G1 phase and induces apoptosis. The underlying mechanisms are ablation of MAPK signaling cascades and increase of caspase activity, respectively. Further through investigation is currently in the process in my laboratory. As characterization of the structure-functional analysis of IGFBP-3 and the IGFBP-3 receptor, we identified differential effects of IGFBP-3 and those IGFBP-3 proteolytic fragments on ligand binding, cell surface association and IGF-I receptor signaling. Current findings under this grant support will provide pivotal evidence for clinical significance and potential application of the IGFBP-3/IGFBP receptor tor axis in the prevention and/or treatment of human neoplasia, in articular, breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA387923
Entities
People
- Youngman Oh
Organizations
- Oregon Health & Science University