Promoter Regions Determining Over-Expression of Metalloproteinase Genes in Breast Cancer
Abstract
The aim of this project is to determine which parts of the matrix metalloproteinase (MMP) genes cause those genes to be over-expressed in breast cancer, contributing to invasion and metastasis. It was determined that breast cancer cells can be classified into two types: one type retains its epithelial characteristics, the other has lost them by undergoing an epithelial-mesenchymal transition (EMT) . The MMPs in each cell type are up- regulated by distinct molecular mechanisms. Gelatinase B is produced at an unusually high level by the epithelial cells, requiring no stimulus from the other cell type. In contrast, the cells that have undergone an EMT up-regulate their MMPs in response to a factor secreted by the epithelial cells. Using MMP promoters linked to measurable reporter genes, it was determined that the constitutively high levels of gelatinase B production are mediated through the region upstream of the proximal promoter, whereas the high inducible levels of MMP production in the cells that have undergone an EMT are not mediated through the upstream regions. Thus, the mechanism determining high MMP production by breast cancer cells depends on the state of differentiation of the cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA384049
Entities
People
- James Lyons
Organizations
- Royal Prince Alfred Hospital