Isolation of Breast Tumor Suppressor Genes from Chromosome lip.
Abstract
We have previously shown that chromosome lip 15.5 exhibits loss of heterozygosity (LOH) in 60% of breast tumors, and that there is a significant correlation between lip LOH, lymphatic invasion and aggressive metastatic disease. Our data suggests that chromosome lip 15.5 harbors a metastasis suppressor gene. An intriguing candidate gene that we have mapped to the metastasis suppressor locus on chromosome lip15.5 is integrin-linked kinase (ILK). ILK is a newly identified ankyrin-repeat containing serine/threonine kinase that binds to the cytoplasmic domains of both Beta 1 and the Beta 3 integrins. Cell-cell and cell-matrix interactions are important prerequisites of the metastatic process and appear to be modulated by cell adhesion receptors called integrins. There is a growing body of evidence suggesting that variations in the expression of these molecules can have a profound effect on tumor biology. In preliminary experiments, we have provided evidence that Integrin-linked kinase expression is down-regulated in primary breast tumors and in cell lines derived from metastatic breast tumors. We have shown that ILK overexpression inhibits the growth of the highly metastatic breast cancer cell line MDA-MB-435. In addition, ILK overexpression stimulates the levels of the growth suppressing integrin alpha5Beta1 and inhibits the levels of alphavBeta3, a growth promoting integrin. These studies suggest that ILK is a breast cancer metastasis suppressor gene.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA378977
Entities
People
- Pratima Karnik