The Cancer/Testis Antigen Melanoma-Associated Antigen-A3/A6 Is a Novel Target of Fibroblast Growth Factor Receptor 2-IIIb through Histone H3 Modifications in Thyroid Cancer
Why this work is in the frame
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Bibliographic record
Abstract
PURPOSE: Fibroblast growth factor (FGF) signals play fundamental roles in development and tumorigenesis. Thyroid cancer is an example of a tumor with nonoverlapping genetic mutations that up-regulate mitogen-activated protein kinase. We reported recently that FGF receptor 2 (FGFR2) is down-regulated through extensive DNA promoter methylation in thyroid cancer. Reexpression of the FGFR2-IIIb isoform impedes signaling upstream of the BRAF/mitogen-activated protein kinase pathway to interrupt tumor progression. In this analysis, we examined a novel target of FGFR2-IIIb signaling, melanoma-associated antigen-A3 and A6 (MAGE-A3/6). EXPERIMENTAL DESIGN: cDNA microarray analysis was done on human WRO thyroid cancer cells transfected with FGFR2-IIIb or empty vector. Identified gene target was confirmed by reverse transcription-PCR and Western blotting. Gene regulation was examined by treatment of WRO cells with the methylation inhibitor 5'-azacytidine followed by methylation-specific PCR and reverse transcription-PCR and by chromatin immunoprecipitation. RESULTS: Gene expression profiling identified the cancer/testis antigen MAGE-A3/6 as a novel target of FGFR2-IIIb signaling. MAGE-A3/6 regulation was mediated through DNA methylation and chromatin modifications. In particular, FGF7/FGFR2-IIIb activation resulted in histone 3 methylation and deacetylation associated with the MAGE-A3/6 promoter to down-regulate gene expression. CONCLUSIONS: These data unmask a complex repertoire of epigenetically controlled signals that govern FGFR2-IIIb and MAGE-A3/6 expression. Our findings provide insights into the interrelationship between novel tumor markers that may also represent overlapping therapeutic targets.
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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 | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.002 | 0.001 |
| 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