Differential Response of Akt to Cyclic AMP Modulates Drug Sensitivity
Bibliographic record
Abstract
Although Akt is known to be associated with drug resistance, its role in cyclic AMP (cAMP)-related inhibition of cell proliferation is not clear. Here, we report that Akt modulates the sensitivity of hepatocellular carcinoma cells to cAMP. Treatment of hepatocellular carcinoma cell lines (HepG(2) and Bel-7402) with cAMP inhibited proliferation, with HepG(2) cells showing lower sensitivity to cAMP. Biochemical studies showed that cAMP increased FBS-stimulated Akt phosphorylation in HepG(2) cells, but completely inhibited FBS-stimulated Akt phosphorylation in Bel-7402 cells, suggesting that the differential response of Akt to cAMP in these two cell lines might contribute to their differential sensitivity. LY294002, a phosphatidylinositol 3-kinase inhibitor that inhibits FBS-stimulated Akt phosphorylation, restored the sensitivity of HepG(2) cells to cAMP and API-2 (Akt/protein kinase B signaling inhibitor-2) also showed similar effect. These results collectively indicate that the response level of Akt to cAMP may play a critical role in determining drug sensitivity.
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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) | 0.001 | 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 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".