Tumor-Derived Ikaros 6 Acetylates the Bcl-XL Promoter to Up-Regulate a Survival Signal in Pituitary Cells
Bibliographic record
Abstract
We reported the expression of the lymphoid zinc finger transcription factor Ikaros (Ik) in the endocrine pituitary gland, where the usual isoforms, Ik1 and Ik2, are thought to play multiple physiological roles. The gene is alternatively spliced to yield a dominant negative isoform, Ik6, in nearly half of human pituitary tumors. We show here that the tumor-specific truncated Ik6 isoform promotes pituitary tumor AtT20 corticotroph and GH4 mammosomatotroph cell growth, evidenced by increased S-phase entry, colony formation in soft agar, and growth of xenografts in vivo. Ik6-mediated cell growth was associated with enhanced protection against apoptosis and up-regulation of the antiapoptotic factor Bcl-XL but not the related Bcl-2 family member. The effect of Ik6 on Bcl-XL induction was not reproduced by small interfering RNA-mediated Ik-down-regulation, indicating that this effect is not mediated entirely by disruption of Ik1 action. In cotransfection studies, Ik1 attenuated and Ik6 enhanced Bcl-XL promoter activity. The effect of Ik6 was mimicked by histone deacetylation inhibition but not by methylation inhibition. Furthermore, chromatin immunoprecipitation confirmed the ability of Ik6 to selectively acetylate histone 3 sites but not influence methylation of the Bcl-XL promoter. Thus, the contribution of Ik6 to tumor pathogenesis involves up-regulation of an antiapoptotic signal generated through selective acetylation of the Bcl-XL promoter.
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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".