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 TUF- 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 TOF. 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. We have also demonstrated the efficacy of the intraductal route to cancer prevention and therapy using the NMU mammary tumor model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADA408748
Entities
People
- Saraswati V. Sukumar
Organizations
- Johns Hopkins University