Prolactin and DNA damage trigger an anti-breast cancer cell immune response
Bibliographic record
Abstract
Introduction The role of prolactin (PRL) in breast cancer and its role within the context of the tumor microenvironment are not well understood. In our previous study, we demonstrated a cross-talk between the ataxia telangiectasia-mutated (ATM) DNA damage response pathway and the PRL-Janus-kinase-2 (JAK2)-signal transducer and activator of transcription-5 (STAT5)-heat shock protein-90 (HSP90) pathway. Here we investigated the role of PRL in tumor initiation and the effect of DNA damage. Methods We used an in vivo model to assess the ability of breast cancer cells to initiate orthotopic xenograft tumor formation after DNA damage. Breast cancer cells engineered to secrete human PRL were treated with the DNA damaging agent doxorubicin and injected into the mammary fat pad of immune-deficient severe combined immunodeficiency disease (SCID) mice. Results Doxorubicin and PRL combination increased the tumor latency, although PRL secretion alone did not change the tumor latency compared to the controls. Depletion of glycolipid asialo ganglioside-GM1-positive immune cells using anti-asialo GM1 antibody resulted in faster tumor formation only in the PRL-secreting breast cancer cells that were pre-treated with doxorubicin. Additionally, doxorubicin plus the PRL treatment of breast cancer cells was shown in vitro to attract cytotoxic NK cells compared to the controls, and this was dependent on the PRLR. Discussion These results demonstrate that combined breast cancer cell DNA damage and PRL exposure results in the anti-tumor cell activity of asialo-GM1-positive immune 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 | 0.000 | 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 | 0.000 |
| 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".