Estrogen and TCDD Influence RLN2 Gene Activity in Estrogen Receptor‐Positive Human Breast Cancer Cells
Bibliographic record
Abstract
Expression of relaxin is increased in human breast cancer, and relaxin was shown to increase in vitro invasiveness through increased production and secretion of matrix metalloproteinases in human breast cancer cells. The role of estrogen in the promotion of breast cancer is well-known. The environmental toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a known carcinogen but has been shown to have antiestrogenic effects in human breast cancer cells. In this study, we have employed real-time PCR and chromatin immunoprecipitation (ChIP) assays to investigate the influence of estrogen and TCDD on relaxin-1 (RLN1) and relaxin-2 (RLN2) gene expression in MCF-7 and T47D human breast cancer cells. Estrogen increased RLN2 transcripts in T47D and MCF-7 cells after just 4 h of exposure, whereas TCDD did not. RLN1 transcripts were only induced after 24 h of estrogen exposure. TCDD did have antiestrogenic activity and reduced the estrogen-mediated increase in RLN2 and RLN1 mRNA. The estrogen-mediated increase in RLN2 mRNA levels was not caused by changes in the mRNA stability. ChIP analysis revealed binding of estrogen receptor-alpha (ERalpha) to promoter sequences of the RLN2 gene. Thus, we provide evidence that RLN2 gene activity is directly regulated by activated ERalpha in human breast cancer cells and we show that activation of the arylhydrocarbon receptor by TCDD inhibits this regulation by estrogen.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".