Abstract 1295: Regulation of PAX2 activity by estradiol in breast cancer cells
Bibliographic record
Abstract
Abstract Most breast cancer deaths arise from tumour cells ability to produce distant metastases. Among breast tumour subtypes, luminal A tumours, which express the highest levels of estrogen receptor alpha, are associated with the poorest metastatic phenotype and with longest relapse-free survival. Usually active during embryogenesis, PAX2, a homeobox transcription factor, is of a particular interest in this context. It is preferentially activated in luminal A tumours in vivo and it was shown to downregulate the expression of ERBB2 (erythroblastic leukemia viral oncogene homolog 2, HER-2/neu), a well-documented proinvasive and pro-metastastic gene, in these cells in response to estradiol in vitro. However, the ability of estradiol to regulate PAX2 activity and ERBB2 expression in non-luminal breast cancer cells, and the intracellular mechanisms involved in estradiol-induced PAX2 activity in breast cancer cells, have not been investigated. Objective: The objective of our work was to compare the impact of estradiol exposure on PAX2 activation in luminal and non-luminal breast cancer cells, and to determine the molecular mechanisms mediating estradiol-induced activation in breast cancer cells. Hypothesis: Estradiol would induce PAX2 activity in breast cancer cells of the luminal subtype only, in an estradiol receptor alpha-dependent manner. Results: Basal PAX2 activity was higher in cell lines from luminal compared to non-luminal subtype. Activation of PAX2 by estradiol, as assessed by measuring PAX2 phosphorylation on serine 393 residue and ERBB2 expression, was selectively achieved in breast cancer cell lines of the luminal subtype. This process was blocked by estrogen receptor alpha antagonist ICI 182780. Conclusion: PAX2 activation by estradiol is selectively achieved in breast cancer cells of the luminal subtype, via ERα. We are currently investigating intracellular signaling pathways downstream of estrogen receptor alpha which could mediate estradiol-induced activation of PAX2 in luminal breast cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1295. doi:1538-7445.AM2012-1295
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".