DNA Cleavage/Repair and Signal Transduction Pathways in Irradiated Breast Tumor Cells
Abstract
We have determined that neither p53 status nor alterations in levels of the Myc protein are critical factors in radiosensitivity or in sensitivity to adriamycin. The refractoriness of breast tumor cells to DNA damage induced apoptosis may be related, in part, to upregulation of p21 as well as to stimulation of MAP kinase activity. Our current studies using cells carrying a p21 antisense vector should clarify the role of p21 while studies relating to the MAP kinase pathway are being initiated. Pretreatment of p53 wild type breast tumor cells with Vitamin D3 compounds sensitizes the cells to ionizing radiation and to adriamycin, in part through the promotion of apoptosis - suggesting that the Vitamin D compounds can be used to enhance the effectiveness of radiotherapy and chemotherapy in the clinical 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, 1999
- Accession Number
- ADA381791
Entities
People
- David A. Gewirtz
Organizations
- Virginia Commonwealth University