Molecular interactions between insulin-like growth factor signal transduction and retinoids in breast cancer cells
Bibliographic record
Abstract
Numerous groups, including ours, have found that retinoids potently inhibit the growth of breast cancer cells, but the mechanisms by which growth regulation is achieved remains unclear. Although several of the effects of retinoids in breast cancer have been linked to the insulin-like growth factor (IGF) system, their effects on key signaling molecules in the IGF type-I receptor (IGF-IR) pathway have not been well characterized. This thesis project examined the hypothesis that retinoids mediate their growth inhibitory effects by targeting specific members of the IGF-IR signal transduction pathway. Although we did not observe regulation of IGF-IR itself, we found that all-trans retinoic acid (RA)-mediated growth inhibition is associated with a selective reduction in insulin receptor substrate 1 (IRS-1) protein and activity levels. We also present evidence that decreasing IRS-1 levels results in the selective down-regulation of the PI 3-kinase/AKT pathway in RA-treated MCF-7 cells. The relevance of IRS-1 regulation to the growth inhibitory action of RA is supported by the results showing that forced expression of IRS-1 abrogates the ability of RA to significantly inhibit MCF-7 cell growth.
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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".