Apolipoprotein E2 modulates cell cycle function to promote proliferation in pancreatic cancer cells via regulation of the c-Myc–p21<sup>Waf1</sup> signalling pathway
Bibliographic record
Abstract
Apolipoprotein E2 (ApoE2) is reportedly critical for cell proliferation and survival, and has been identified as a potential tumour-associated marker in many kinds of cancer. However, studies of the function and mechanisms of ApoE2 in pancreatic cancer proliferation and development are rare. In this study, we performed an analysis to determine the modulatory effects of ApoE2–LRP8 (lipoprotein receptor-related protein 8) pathway on cell cycle and cell proliferation, and explored its mechanisms in pancreatic cancer. High expression levels of ApoE2–LRP8/c-Myc were detected in tumour tissues and cell lines by immunohistochemistry and Western blotting. It was also shown that ApoE2–LRP8 induced phosphorylation of ERK1/2 to activate c-Myc and contribute to cell-cycle-related protein expression. ApoE2 conditions induced c-Myc binding to target gene sequences in the p21Waf1 promoter, resulting in decreased transcription. ERK/c-Myc contributes to the promotion of the expression levels of cyclin D1, cdc2, and cyclin B1, and reduces p21Waf1 activity, thereby promoting cell cycle distribution. We demonstrated the function of ApoE2–LRP8 in the activation of the ERK–c-Myc–p21Waf1 signalling cascade and the modulation of G1/S and G2/M transition, indicating ApoE2–LRP8’s important role in the cancer cell proliferation. ApoE2 could serve as a diagnostic marker and chemotherapeutic target in pancreatic cancer.
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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".