ArticleMolecular and cellular biology2005
Deregulated E2F activity induces hyperplasia and senescence-like features in the mouse pituitary gland.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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96 citing papers in PubMed, 186 citations in OpenAlex.
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- Melatonin Exerts Prominent, Differential Epidermal and Dermal Anti-Aging Properties in Aged Human Eyelid Skin Ex Vivo.International journal of molecular sciences · 2023Article
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- Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications.Journal of hematology & oncology · 2023Review
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- The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis.Cells · 2022Review
- Cellular Senescence in Aging Lungs and Diseases.Cells · 2022Review
- Mechanisms of Cell Cycle Arrest and Apoptosis in Glioblastoma.Biomedicines · 2022Review
- Architects of Pituitary Tumour Growth.Frontiers in endocrinology · 2022Review
- Schleichera oleosa Seed Extract Reduced the Proliferation of Breast Cancer by Regulating the BRCA1 and p16 Genes.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Senescence-Associated Molecules and Tumor-Immune-Interactions as Prognostic Biomarkers in Colorectal Cancer.Frontiers in medicine · 2022Article
- Cellular senescence in cancer: from mechanisms to detection.Molecular oncology · 2021Review
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- Cellular senescence or stemness: hypoxia flips the coin.Journal of experimental & clinical cancer research : CR · 2021Review
- Cell senescence in neuropathology: A focus on neurodegeneration and tumours.Neuropathology and applied neurobiology · 2021Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The retinoblastoma gene, RB1, is one of the most frequently mutated genes in human cancer. Rb heterozygous mice develop pituitary tumors with 100% incidence, and the E2F transcription factors are required for this. To assess whether deregulated E2F activity is sufficient to induce pituitary tumors, we generated transgenic mice expressing an inducible E2F3 protein in the intermediate lobe of the pituitary gland. We found that short-term deregulation of E2F activity, similar to the earliest stages of Rb loss, is able to induce abnormal proliferation of otherwise quiescent melanotrophs. However, while long-term exposure to deregulated E2F activity results in hyperplasia of the intermediate lobe, it did not lead to tumor formation. In fact, melanotrophs become insensitive to sustained E2F stimulation and enter an irreversible senescence-like state. Thus, although deregulated E2F activity results in hyperproliferation, it is not sufficient to mimic loss of Rb, sustain proliferation of melanotrophs, and ultimately induce pituitary tumors. Similarly, we found that primary cells in tissue culture become insensitive to sustained E2F3 activation and undergo premature senescence in a pRB-, p16Ink4a-, and p19Arf-dependent manner. Thus, we conclude that deregulated E2F activity is not sufficient to fully mimic loss of Rb due to the engagement of a senescence response.
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