| A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen. | |
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MedLine Citation:
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PMID: 20169192 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cellular senescence irreversibly arrests cell proliferation in response to oncogenic stimuli. Human cells develop a senescence-associated secretory phenotype (SASP), which increases the secretion of cytokines and other factors that alter the behavior of neighboring cells. We show here that "senescent" mouse fibroblasts, which arrested growth after repeated passage under standard culture conditions (20% oxygen), do not express a human-like SASP, and differ from similarly cultured human cells in other respects. However, when cultured in physiological (3%) oxygen and induced to senesce by radiation, mouse cells more closely resemble human cells, including expression of a robust SASP. We describe two new aspects of the human and mouse SASPs. First, cells from both species upregulated the expression and secretion of several matrix metalloproteinases, which comprise a conserved genomic cluster. Second, for both species, the ability to promote the growth of premalignant epithelial cells was due primarily to the conserved SASP factor CXCL-1/KC/GRO-alpha. Further, mouse fibroblasts made senescent in 3%, but not 20%, oxygen promoted epithelial tumorigenesis in mouse xenographs. Our findings underscore critical mouse-human differences in oxygen sensitivity, identify conditions to use mouse cells to model human cellular senescence, and reveal novel conserved features of the SASP. |
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Authors:
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Jean-Philippe Coppé; Christopher K Patil; Francis Rodier; Ana Krtolica; Christian M Beauséjour; Simona Parrinello; J Graeme Hodgson; Koei Chin; Pierre-Yves Desprez; Judith Campisi |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-02-12 |
Journal Detail:
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Title: PloS one Volume: 5 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2010 |
Date Detail:
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Created Date: 2010-02-19 Completed Date: 2010-09-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
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Languages: eng Pagination: e9188 Citation Subset: IM |
Affiliation:
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Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Cell Aging / genetics, physiology* Cells, Cultured DNA Damage Epithelial Cells / metabolism, physiology, secretion Fibroblasts / metabolism, physiology*, secretion Genomic Instability Humans Insulin-Like Growth Factor Binding Protein 6 / genetics, metabolism Interleukin-6 / genetics, metabolism Intracellular Signaling Peptides and Proteins / genetics, metabolism Matrix Metalloproteinases / genetics, metabolism Mice Mice, Inbred C57BL Mice, Nude Neoplasms, Experimental / genetics, metabolism, pathology Oxygen / metabolism, physiology* Phenotype Proteome / genetics, metabolism* Proteomics / methods Reverse Transcriptase Polymerase Chain Reaction Species Specificity Transplantation, Heterologous Tumor Burden |
| Grant Support | |
ID/Acronym/Agency:
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AG000266/AG/NIA NIH HHS; AG0025708/AG/NIA NIH HHS; AG017242/AG/NIA NIH HHS; AG09909/AG/NIA NIH HHS; CA126540/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Insulin-Like Growth Factor Binding Protein 6; 0/Interleukin-6; 0/Intracellular Signaling Peptides and Proteins; 0/Proteome; 0/Trp53bp1 protein, mouse; 7782-44-7/Oxygen; EC 3.4.24.-/Matrix Metalloproteinases |
| Comments/Corrections | |
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