PURPOSE: To test the hypothesis that breast cancer patients could have a predisposing defect in the induction of TP53 tumor suppressor protein (known as p53) that could be a marker of genetic instability and increased cancer susceptibility. The accumulation of p53 was triggered by ionizing radiation, and its transcriptional activity was estimated from the induction of CDKN1A (known as p21).METHODS AND MATERIALS: Using Western blot, we studied the radiation induction of p53 and p21 proteins in 28 fibroblast cell strains derived from 7 healthy donors (Control), 3 ataxia telangiectasia (AT), 3 AT heterozygous, and 15 breast cancer patients. Contact-inhibited plateau phase cells were irradiated with 6 Gy, and proteins were assessed 3, 6, and 24 h later.RESULTS: The control group showed a high induction of p53 at 3 h postirradiation followed by a relative decrease at 6 h, and approached the basal level at 24 h. This was associated with a parallel induction in p21. The response of fibroblasts derived from the breast cancer group was not significantly different from the control. Similar results were obtained with the AT heterozygous group at 3 h postirradiation; however, sustainable increase in p53 and p21 induction was observed at 24 h. AT cells showed a statistically significant highly reduced accumulation of p53 and a delayed and reduced induction of p21 (p < or = 0.05). Furthermore, a correlation was observed between these two proteins at the 3-h induction point, confirming the high dependence of p21 on p53.CONCLUSION: Although severe deficiency in p53 and p21 induction was observed in fibroblasts derived from the cancer-prone AT syndrome, these results do not support the assumption that breast cancer patients have a predisposing defective induction in these proteins after ionizing irradiation.
Ataxia Telangiectasia Breast Neoplasms