SUN-011 Identification Of Regulators Of Estrogenic Signalling In ER-positive Breast Cancer Cells By Whole Genome shRNA Screening
Bibliographic record
Abstract
Over 70% of breast tumours express estrogen receptor alpha (ERα), a ligand-inducible transcription factor. Stimulation with estradiol leads to receptor binding to estrogen response elements (EREs) in target genes regulatory sequences in association with transcriptional cofactors. This results in altered gene expression, increased cell proliferation and accelerated tumour growth. To systematically identify genes contributing to ERα expression and signalling in breast cancer, we performed a genome-wide screen in human ERα+ luminal breast cancer cell lines stably expressing estrogen-induced luciferase reporters using an arrayed format. A primary screen (Sigma Mission lentiviral library, 16083 genes, three shRNA/gene) and secondary screens (615 genes identified as hits by at least two shRNAs with concordant impact on reporter gene expression without major effects on cell survival) were carried out using estrogen-sensitive cells (T47D-ERE3-Luc, MCF-7-ERE-Luc) and insensitive controls (antioxidant response reporter T47D-ARE-Luc). We ultimately characterized by RNASeq the impact of suppressing expression of each of 30 prioritized hits (2-3 shRNAs with >50% reduction of RNA levels per hit) on gene expression in ERα+ breast cancer cells. Knockdown of several of these hits had extensive impacts on expression of direct estrogen target genes and on ERα+ breast cancer cell proliferation. Some hits regulated ERα gene expression and several interacted with ERα in co-IP experiments, indicating roles as upstream regulators and/or transcriptional cofactors of ERα.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".