DNA Cleavage/Repair and Signal Transduction Pathways in Irradiated Breast Tumor Cells.
Abstract
Studies were designed to understand the role of the p53, Myc, p21waf1/cip1, Rb and E2F proteins (as well as the Bax and Bcl-2 proteins) in the pathway leading to growth arrest and apoptotic cell death in the breast tumor cell. We have determined that neither p53 status nor alterations in levels of the Myc protein are critical factors in radiosensitivity. Furthermore, the absence of apoptosis cannot be related to lack of p53/E2F-1 or p53/Myc interactions or to changes in Bax or Bcl-2. Pretreatment of p53 wild type breast tumor cells with Vitamin D3 compounds sensitizes the cells to ionizing radiation - suggesting a role for the combination of Vitamin D3 compounds with radiotherapy in the treatment of breast cancer. Irradiation can also enhance the efficiency of liposomal mediated transgene uptake suggesting that irradiation could be combined with gene therapy in the treatment of breast cancer. Finally, we are attempting to determine how p53 status influences the fidelity of double-strand break repair in apoptosis-proficient 184B5 breast epithelial cells, and the possible relation between apoptosis and tolerance for misrepair. Such studies may suggest additional candidates for transgenic manipulation of the response to radiation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADA358103
Entities
People
- David A. Gewirtz
Organizations
- Virginia Commonwealth University