GLYCOGEN SYNTHASE KINASE-3 (GSK3) ACTIVITY PLAYS CRUCIAL ROLE IN HUMAN PANCREATIC CANCER CELL PROLIFERATION AND SURVIVAL
Bibliographic record
Abstract
Background: GSK3 is a serine/threonine kinase that was first identified for its role in glycogen metabolism. Beyond that, we now know that it also plays an important role in other cellular processes such as cell proliferation, survival and transformation. However, cellular context greatly influence its contribution to these different cellular processes. Aim: To evaluate the contribution of the GSK3 activity in proliferation and survival of human pancreatic cancer cells. Methods: Different cell lines were used (PANC-1, MIA PaCa-2, BxPC-3) and treated with specific GSK3 inhibitors (SB216763, AR-A014418). Results: 1- During G1-S phase progression, low GSK3 activity was initially observed, but GSK3 was reactivated in mid-G1 up to the S phase of the cell cycle. 2- Inhibition of GSK3 activity from mid-G1 to the S phase (when GSK3 is typically reactivated) was sufficient to block pRb hyperphosphorylation. 3- Moreover, prolonged inhibition of GSK3 (48/72 h) induced PARP cleavage and caspase-7 activation. 4- This apoptotic response was associated with increased Bim and reduced Bcl-2 protein levels. 5- A 48 h recovery period (in normal cultured medium) following a 24 h SB216763 treatment was unable to protect the cells against apoptosis. Conclusion: Taking together, these results suggest that GSK3 participates in human pancreatic cancer cell proliferation, especially in late G1-S phase progression of the cell cycle. In addition, GSK3 activity plays a crucial role in cell survival as inhibition of GSK3 activity for 24 h is sufficient to induce irreversible cell death.
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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".