Identification of Hepatocyte Growth Factor Autocrine Loops in Breast Carcinomas: Possible Target for Therapeuti Intervention
Abstract
We previously demonstrated elevated HGF and Met expression in regions of invasive human breast carcinomas, suggesting a role of autocrine HGF loops in invasive breast cancer. We have now demonstrated that: (a) elevated HGF and Met expression occurs in some newly-derived breast and non-small cell lung carcinoma cell lines; and (b) three carcinoma cell lines showed autocrine tyrosine-phosphorylation of Met and increased cell survival, consistent with the presence of autocrine HOE loops. These findings suggest that targeting autocrine HOE loops is an important strategy for therapeutic intervention in breast cancer metastasis. Based on 3-D computer modelling of the Met receptor binding site in the K1 kringle domain of HOE, we have initiated a phage display approach to screen 7-lO mer peptide libraries for putative peptide antagonists of HOE that block ligand receptor binding. These putative peptide antagonists will be isolated, and tested for the ability to inhibit tumorigenesis and metastasis of breast carcinoma cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA388861
Entities
People
- Jin Gui
- Peter Greer
Organizations
- Queen's University