Promotion of apoptosis (which is frequently dependent on functional p53) is thought to be critical for the effectiveness of chemotherapy or radiotherapy. Studies in this as well as other laboratories have demonstrated that breast tumor cells are relatively refractory to apoptosis in response to modalities that induce DNA damage. This report describes our efforts to understand the basis for the absence of an apoptotic response to adriamycin and ionizing radiation in the breast tumor cell based on alterations in cell-cycle and apoptotic regulatory proteins. We also report on the permissive effects of Vitamin D3 and the Vitamin D3 analog EB 1089 in the promotion of apoptosis in p53-wild-type cells. Our studies suggest that regulation of apoptosis in the breast tumor cell may require modulation of signaling events other than or in addition to the p53-dependent DNA damage response.
These findings suggest that in the absence of classical apoptotic cell death, radiosensitivity is not predictably related to the p53 status of the cell. While both p53 and c-myc may be linked to the DNA damage response pathway, neither p53 nor c-myc are essential for growth arrest in response to ionizing radiation.
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