| Growth stimulation leads to cellular senescence when the cell cycle is blocked. | |
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MedLine Citation:
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PMID: 18948731 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We tested a hypothesis that activation of growth-promoting pathways is required for cellular senescence. In the presence of serum, induction of p21 caused senescence, characterized by beta-Galactosidase staining, cell hypertrophy, increased levels of cyclin D1 and active TOR (target of rapamycin, also known as mTOR). Serum starvation and rapamycin inhibited TOR and prevented the expression of some senescent markers, despite high levels of p21 and cell cycle arrest. In the presence of serum, p21-arrested cells irreversibly lost proliferative potential. In contrast, when cells were arrested by p21 in the absence of serum, they retained the capacity to resume proliferation upon termination of p21 induction. In normal human cells such as WI38 fibroblasts and retinal pigment epithelial (RPE) cells, serum starvation caused quiescence, which was associated with low levels of cyclin D1, inactive TOR and slim-cell morphology. In contrast, cellular senescence with high levels of TOR activity was induced by doxorubicin (DOX), a DNA damaging agent, in the presence of serum. Inhibition of TOR partially prevented senescent phenotype caused by DOX. Thus growth stimulation coupled with cell cycle arrest leads to senescence, whereas quiescence (a condition with inactive TOR) prevents senescence. |
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Authors:
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Zoya N Demidenko; Mikhail V Blagosklonny |
Publication Detail:
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Type: Journal Article Date: 2008-11-12 |
Journal Detail:
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Title: Cell cycle (Georgetown, Tex.) Volume: 7 ISSN: 1551-4005 ISO Abbreviation: Cell Cycle Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2008-12-23 Completed Date: 2009-02-10 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 101137841 Medline TA: Cell Cycle Country: United States |
Other Details:
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Languages: eng Pagination: 3355-61 Citation Subset: IM |
Affiliation:
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Oncotarget, Albany, New York, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Aging*
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drug effects Cell Cycle* / drug effects Cell Line Cell Proliferation / drug effects Cell Shape / drug effects Colony-Forming Units Assay Cyclin D1 / metabolism Cyclin-Dependent Kinase Inhibitor p21 / metabolism Doxorubicin / pharmacology Fibroblasts / cytology, drug effects Humans Isopropyl Thiogalactoside / pharmacology Models, Biological Phenotype Protein Kinases / metabolism Serum Sirolimus / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Cyclin-Dependent Kinase Inhibitor p21; 136601-57-5/Cyclin D1; 23214-92-8/Doxorubicin; 367-93-1/Isopropyl Thiogalactoside; 53123-88-9/Sirolimus; EC 2.7.-/Protein Kinases; EC 2.7.1.-/mTOR protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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