Estrogen regulated expression of the p21<sup>Waf1/Cip1</sup> gene in estrogen receptor positive human breast cancer cells
Bibliographic record
Abstract
The cyclin-dependent kinase inhibitor protein p21(Waf1/Cip1) is a potent tumor suppressor. Here, we demonstrate that estradiol regulates the p21(Waf1/Cip1) gene. Estradiol induces p21(Waf1/Cip1) mRNA expression within 30-60 min independent of new protein synthesis in the estrogen receptor alpha (ER alpha) positive human breast cancer cell line MCF-7. Similar to other estradiol responsive promoters, the p21(Waf1/Cip1) upstream promoter region has several estrogen response element (ERE) half-sites nestled in AP-1 binding sites, which are positioned upstream to Sp1 binding sites. Using the chromatin immunoprecipitation (ChIP) assay, we show that estradiol stimulation resulted in the recruitment of transcription factors ER alpha, Sp1, and Sp3 to the p21(Waf1/Cip1) upstream promoter element. The Sp1 inhibitor mithramycin A abrogated Sp1, and to a lesser extent Sp3 binding, and markedly reduced the estradiol stimulated p21(Waf1/Cip1) gene expression. However, ER alpha binding was not affected in the mithramycin A and estradiol treated cells. On closer examination of the half-site ERE/AP-1 sites upstream to the Sp1 sites in a separate ChIP experiment, we found a pronounced association of ER alpha upon estradiol treatment compared to almost negligible binding of Sp1 or Sp3. Together these studies provide evidence that ER alpha is recruited to the half-site ERE/AP-1 sites in the p21(Waf1/Cip1) upstream promoter element. Although Sp1/Sp3 is not involved in the recruitment of ER alpha to the promoter, Sp1 is necessary for estrogen-induced p21(Waf1/Cip1) promoter activity.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.000 | 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".