ArticleProceedings of the National Academy of Sciences of the United States of America2008
p21(Cip1) restrains pituitary tumor growth.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02160730 (Treatment of Pituitary Cushing Disease With a Selective CDK Inhibitor, R-roscovitine), which is not on this map. Cited by 63 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Treatment of Pituitary Cushing Disease With a Selective CDK Inhibitor, R-roscovitine
Who cites it
63 citing papers in PubMed, 2 syntheses or guidelines pooled it, 140 citations in OpenAlex.
- Genetic aspects of pituitary carcinoma: A systematic review.Medicine · 2016Pooled it
- Correlations of pituitary tumor transforming gene expression with human pituitary adenomas: a meta-analysis.PloS one · 2014Pooled it
- STING expression in pituitary neuroendocrine tumour immune microenvironments.Endocrine-related cancer · 2026Article
- Pathogenesis of nonfamilial somatotroph adenomas.The Journal of clinical endocrinology and metabolism · 2026Review
- Impact of acromegaly subtypes on survival: results from a large multicenter cohort.Journal of the Endocrine Society · 2026Article
- The role of methylation in pituitary neuroendocrine tumors current insights and emerging perspectives.Molecular biology reports · 2026Review
- New insights in cellular senescence: The pituitary model.Journal of neuroendocrinology · 2025Review
- Relationship between Pituitary Gland and Stem Cell in the Aspect of Hormone Production and Disease Prevention: A Narrative Review.Endocrine, metabolic & immune disorders drug targets · 2025Review
- Multiomics Approach to Acromegaly: Unveiling Translational Insights for Precision Medicine.Endocrinology and metabolism (Seoul, Korea) · 2023Review
- Clinical Biology of the Pituitary Adenoma.Endocrine reviews · 2022Review
- GH and Senescence: A New Understanding of Adult GH Action.Journal of the Endocrine Society · 2022Review
- Molecular targets in acromegaly.Frontiers in endocrinology · 2022Review
- Architects of Pituitary Tumour Growth.Frontiers in endocrinology · 2022Review
- Iodoacetic Acid, a Water Disinfection Byproduct, Disrupts Hypothalamic, and Pituitary Reproductive Regulatory Factors and Induces Toxicity in the Female Pituitary.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Role of ARK5 in cancer and other diseases (Review).Experimental and therapeutic medicine · 2021Review
- Adamantinomatous craniopharyngioma as a model to understand paracrine and senescence-induced tumourigenesis.Cellular and molecular life sciences : CMLS · 2021Review
- DNA damage and growth hormone hypersecretion in pituitary somatotroph adenomas.The Journal of clinical investigation · 2020Article
- Genistein inhibits proliferation and induces senescence in neonatal mouse pituitary gland explant cultures.Toxicology · 2019Article
- Antibody array strategy for human growth factor secretome profiling of GH-secreting adenomas.Pituitary · 2019Article
- HMGA2 cooperates with either p27Cell cycle (Georgetown, Tex.) · 2018Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
As commonly encountered, pituitary adenomas are invariably benign. We therefore studied protective pituitary proliferative mechanisms. Pituitary tumor transforming gene (Pttg) deletion results in pituitary p21 induction and abrogates tumor development in Rb(+/-)Pttg(-/-) mice. p21 disruption restores attenuated Rb(+/-)Pttg(-/-) pituitary proliferation rates and enables high penetrance of pituitary, but not thyroid, tumor growth in triple mutant animals (88% of Rb(+/-) and 72% of Rb(+/-)Pttg(-/-)p21(-/-) vs. 30% of Rb(+/-)Pttg(-/-) mice developed pituitary tumors, P < 0.001). p21 deletion also accelerated S-phase entry and enhanced transformation rates in triple mutant MEFs. Intranuclear p21 accumulates in Pttg-null aneuploid GH-secreting cells, and GH(3) rat pituitary tumor cells overexpressing PTTG also exhibited increased levels of mRNA for both p21 (18-fold, P < 0.01) and ATM (9-fold, P < 0.01). PTTG is abundantly expressed in human pituitary tumors, and in 23 of 26 GH-producing pituitary adenomas with high PTTG levels, senescence was evidenced by increased p21 and SA-beta-galactosidase. Thus, either deletion or overexpression of Pttg promotes pituitary cell aneuploidy and p53/p21-dependent senescence, particularly in GH-secreting cells. Aneuploid pituitary cell p21 may constrain pituitary tumor growth, thus accounting for the very low incidence of pituitary carcinomas.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.