Transfection of p27<sup>Kip1</sup> Threonine Residue 187 Mutant Type Gene, Which Is Not Influenced by Ubiquitin-Mediated Degradation, Induces Cell Cycle Arrest in Oral Squamous Cell Carcinoma Cells
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Bibliographic record
Abstract
<i>Objective:</i> It is well known that reduction of the cyclin-dependent kinase inhibitor p27<sup>Kip1</sup> protein correlates with the malignant behavior of various cancers including oral squamous cell carcinoma (OSCC). The loss of p27<sup>Kip1</sup> protein is suggested to be due to the enhancement of its posttranslational degradation. In the present study, to evaluate the effects of p27<sup>Kip1</sup> transfection on the cell cycle, we transfected OSCC cell lines with a high activity of p27<sup>Kip1</sup> degradation with p27<sup>Kip1</sup> threonine 187-to-alanine (T187A) mutant gene, which is not influenced by ubiquitin-mediated degradation, as well as with wild type gene. <i>Methods:</i> We transfected p27<sup>Kip1</sup> T187A mutant and wild type gene into OSCC cell lines (HSC2 and HSC3) by using an ecdysone-inducible gene expression system. <i>Results:</i> After treatment with ponasterone A, we could find an induction of both p27<sup>Kip1</sup> wild type and T187A mutant protein. Both wild type and T187A mutant protein induced by 5 µ<i>M</i> ponasterone A inhibited cell growth and increased cell number at the G1 phase. After treatment with 1 µ<i>M</i> ponasterone A, ectopic p27<sup>Kip1</sup> protein was degraded in wild type clones, but not in T187A mutant clones. Moreover, transfection of the T187A mutant gene was more effective in inhibiting cell growth even by induction of a small amount of protein. <i>Conclusion:</i> We suggest that the transfection of the p27<sup>Kip1</sup> T187A mutant gene can be a modality of cancer gene therapy for OSCC.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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 it