Role of IGFBP-3/IGFBP-3 Receptor Interacton in Normal and Malignant Mammary Growth
Abstract
This report will detail the investigations of my laboratory into the biological actions of insulin-like growth factor binding protein 3 (IGFBP-3), which has been shown to exhibit activity in an IGF-independent manner. Data indicate that IGFBP-3 alone can bind to breast cancer cell surfaces, and subsequently exert inhibitory effects on cell growth. We have isolated, cloned, expressed, and purified a novel IGFBP-3 interacting protein, clone 4-33, and demonstrated a specific interaction with IGFBP-3 in a human breast cancer cell system. Further, transient overexpression of clone 4-33 in breast cancer cells results in an increase in the specific binding of IGFBP-3 to the cell surface. To facilitate more detailed investigation into the interaction and functions of these two proteins, we have generated a polyclonal oc4-33 antibody which is specific and functional in a variety of immunoassays. Also to this end, we have generated IGFBP-3 stably transfected human breast cancer cell lines, in which expression of IGFBP-3 is inducible. Additionally, we have localized the IGFBP-3 receptor binding domain within the midregion of the IGFBP-3 molecule, residues 88-148. Further, we have examined naturally occurring and generated synthetic IGFBP-3 proteolytic fragments, and characterized IGF and insulin binding affinity compared to intact IGFBP-3.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADB255775
Entities
People
- Youngman Oh
Organizations
- Oregon Health & Science University