Prevention of Breast Cancer by Targeted Disruption of Breast Epithelial Cells
Abstract
We proposed to test the validity of the hypothesis that introduction of recombinant toxins into the confines of the mammary ductal tree through the teat will kill breast epithelial cells. The toxins TGF-alpha and Heregulin-linked Pseudomonas exotoxin would be tested in the rat MNU-induced mammary tumor model. In the first year, we injected varying amounts of the TGF-a/PE and the Heregulin/PE toxin in rats by the intraductal route. While the toxin was extremely potent in human normal and breast cancer cells in culture, it was ineffective in killing the rat ductal cells. Although highly conserved, the human ligands do not appear to bind to the rodent receptors. We needed to design new toxins to target rat cells. We have completed the construction of a chimeric toxin consisting of the protein transduction domain of the HIV TAT gene to target and enter the cells, and the VPR gene of HIV to cause apoptosis. Expression of this protein in bacteria, and its purification is in progress. In the second year of this grant we will test the efficacy of this toxin in cultured human and rat breast cells. If effective, we will test the toxin in the rat model system.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA386752
Entities
People
- Saraswati Sukumar
Organizations
- Johns Hopkins University