Cyclin D1 Is a Direct Target of JAG-Mediated Notch Signaling in Breast Cancer.
Bibliographic record
Abstract
Abstract We have previously demonstrated that expression of the Notch ligand, JAG1 is associated with the basal breast cancer phenotype and disease recurrence. Herein we report on a genomics approach to elucidate mechanisms downstream of JAG1 that promote breast cancer growth. In a survey of 46 breast cancer cell lines we found that triple negative (TN; basal and mesenchymal ER-, PR- and Her2-negative) lines express JAG1 at significantly higher levels than do HER2+ or luminal (ER+) Her2- cell lines. The TN breast cancer cell lines HCC1143 and MDA MB231, which express JAG1 and demonstrate growth inhibition with RNA interference-induced down-regulation of JAG1, were selected for further study. We used microarray profiling of tumor cells transfected with JAG1 siRNA to identify JAG1-regulated genes. Differentially expressed genes (p ≤ 0.005; fold change ≥ 1.5) were identified for further study. Among the JAG1-regulated genes identified, cyclin D1 was found to be a direct target of NOTCH1 and NOTCH3. We show that JAG1 down-regulation results in reduced cyclin D1 expression, reduced direct binding of Notch to the cyclin D1 promoter, and inhibition of cell cycle progression through the cyclin D1-dependant G1/S check-point. Furthermore, we show that cyclin D1 and JAG1 expression correlate in basal breast cancer expression data sets. These data suggest a model whereby JAG1 promotes cyclin D1-mediated proliferation of TN breast cancer cells. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2150.
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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) | 0.001 | 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".