p53 Activation in Chronic Radiation-Treated Breast Cancer Cells
Bibliographic record
Abstract
Mammalian cells chronically exposed to ionizing radiation (IR) induce stress response with a tolerance to the subsequent cytotoxicity of IR. Although p53 is well documented in IR response, the signaling network causing p53 activation in chronic IR remains to be identified. Using breast carcinoma MCF+FIR cells that showed a transient radioresistance after exposure chronically to fractionated IR (FIR), the present study shows that the basal DNA binding and transcriptional activity of p53 was elevated by FIR. p53-controlled luciferase activity was strikingly induced ( approximately 7.9-fold) with little enhancement of p53/DNA binding activity ( approximately 1.3-fold). The phosphorylated p53 (Thr 55) was increased in the cytoplasm and nucleus of MCF+FIR but not in the sham-FIR control cells. On the contrary, the sham-FIR control MCF-7 cells showed a low p53 luciferase transcription ( approximately 3-fold) but a striking enhancement of p53/DNA binding (12-fold) after 5 Gy of IR. To determine the signaling elements regulating p53 activity, DNA microarray of MCF+FIR using sham-FIR MCF-7 cells as a reference demonstrated that the mRNA of p21, MDM2, and p14ARF was up-regulated. Time course Western blot analysis, however, showed no difference in p21 induction. In contrast, MDM2 that was absent in control cells and was predominantly induced by IR was not induced in MCF+FIR cells. In agreement with MDM2 inhibition, MDM2-inhibitory protein p14ARF was increased in MCF+FIR cells. In summary, these results demonstrate that up-regulation of p14ARF paralleled with MDM2 inhibition contributes to p53 accumulation in the nucleus and causes a high responsiveness of p53 in chronic IR-treated breast cancer cells.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".