PAI-1 Gene as a Target for Breast Cancer Therapy
Abstract
The purpose of work in year 02 of this study was to define the in vitro growth characteristics of stable lines of human breast carcinoma cells (developed in year 01) that expressed varying levels of plasminogen activator inhibitor type-l (PAI-l) as a result of transfection with vectors bearing PAI-l cDNA inserts cloned in the sense and antisense orientations. A panel of 18 such genetically-engineered epithelial cells was created. Eight of these cell lines were completely assessed as to their ability (1) to adhere to surfaces coated with various extracellular matrix proteins (adhesion assay), (2) to locomote across a planar surface following scrape-injury of a confluent monolayer (directed cell migration), and (3) to exhibit motile growth behavior in invasion chamber assays. PAT-l expression was required for epithelial cell migration in directed assays since antisense targeting of PAI-l transcripts reduced both cell adhesion and locomotion on extracellular matrices. A "window" level of PAI-l expression was necessary for optimal epithelial cell locomotion and invasive migration. These data support the hypothesis that PAI-l synthesis is necessary for invasive motility and metastatic behavior of human breast cancer cells. Work in year 03 will test this hypothesis in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2000
- Accession Number
- ADA389515
Entities
People
- Paul Higgins
Organizations
- Albany Medical College