Evaluation of DNA Binding as Inhibitors of ESX, and ETS Domain Transcription Factor Associated with Breast Cancer: Effects of ESX/DNA Complex Disruption
Abstract
DNA binding agents are being evaluated for their ability to disrupt transcription factor binding to DNA and down regulate cancer associated gene expression. Target gene is HER2/neu, which is overexpressed in 30% of breast cancers. Drugs with different modes of binding as well as different sequence preference are being evaluated. Polyamides, a novel group of DNA binding agents with sequence specific binding, are also under evaluation. Cell-free assays such as mobility shift and cell-free transcription are being employed to assess agents' ability to disrupt transcription factor binding. Agents showing potential in cell-free assays were evaluated in whole cell assays using northern analysis. Results in mobility shift assay indicate that sequence specific binding agents inhibit transcription factor DNA complexes better the sequence preference agents by an order of magnitude. In cell-free transcription assays there is less difference between the two types of drugs. Some sequence preference agents are very effective at inhibiting gene expression in whole cells, while first generation polyamides show limited ability to diminish gene expression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADB258871
Entities
People
- Stephanie J. Leslie
Organizations
- Health Research, Incorporated