Senescence Mediates Pituitary Hypoplasia and Restrains Pituitary Tumor Growth
Bibliographic record
Abstract
Understanding factors subserving pituitary cell proliferation enables understanding mechanisms underlying uniquely benign pituitary tumors. Pituitary tumor-transforming gene (Pttg) deletion results in pituitary hypoplasia, low pituitary cell proliferation rates, and rescue of pituitary tumor development in Rb(+/-) mice. Pttg(-/-) pituitary glands exhibit ARF/p53/p21-dependent senescence pathway activation evidenced by up-regulated p19, cyclin D1, and Bcl-2 protein levels and p53 stabilization. High pituitary p21 levels in the absence of PTTG were associated with suppressed cyclin-dependent kinase 2 activity, Rb phosphorylation, and cyclin A expression, all required for cell cycle progression. Although senescence-associated beta-galactosidase was enhanced in Pttg-deficient pituitary glands, telomere lengths were increased. DNA damage signaling pathways were activated and aneuploidy was evident in the Pttg-deficient pituitary, triggering senescence-associated genes. To confirm the p21 dependency of decreased proliferation and senescence in the Pttg-null pituitary, mouse embryonic fibroblast (MEF) colony formation was tested in wild-type, Pttg(-/-), Rb(+/-), Rb(+/-)Pttg(-/-), and Rb(+/-)Pttg(-/-)p21(-/-) cells. Rb(+/-)Pttg(-/-) MEFs, unlike Rb(+/-) cells, failed to produce colonies and exhibited high levels of senescence. p21 deletion from Rb(+/-)Pttg(-/-) MEFs enhanced anchorage-independent cell growth, accompanied by a marked decrease in senescence. As cell proliferation assessed by bromodeoxyuridine incorporation was higher in Rb(+/-)Pttg(-/-)p21(-/-) relative to Rb(+/-)Pttg(-/-) pituitary glands, p21-dependent senescence provoked by Pttg deletion may underlie pituitary hypoplasia and decreased tumor development in Rb(+/-)Pttg(-/-) mice.
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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 | 0.001 |
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".