PAI-1 Gene as a Target for Breast Cancer Therapy
Abstract
This final report details in vitro and in vivo growth characteristics of stable lines of human breast carcinoma cells (developed throughout this study) that synthesized varying levels of plasminogen activator inhibitor type-1 (PAI-1) as a result of transfection with expression vectors bearing PAI-1 cDNA inserts cloned in sense and antisense orientations. A selected set of tumor cell lines (based on level of PAI-1 expression perturbation) was completely characterized with regard to specific in vitro motile traits (chemokinesis, chemotaxis, 2-D planar migration, barrier invasion). PAI-1 synthesis was required for tumor cell migration in directed as says since anti sense targeting effectively suppressed cell motility. These results were confirmed with neutralizing PAI-1 antibodies and exogenously-supplied recombinant PAI-1 protein. A expression vector was created in which PAI-1 promoter sequences were used to drive expression of a chimeric PAI-1-GFP insert. This vector confirmed PAI-1 expression in locomoting cells and PAI-1 deposition into migration trails suggesting its use as a tool to track metastatic tumor cells in vivo. PAI-1 down-regulation slowed human breast cancer implant growth in nude mice and inhibited lung colonization suggesting a therapeutic benefit to PAI-1 gene targeting.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2002
- Accession Number
- ADA407489
Entities
People
- Paul J. Higgins
Organizations
- Albany Medical College