| Oncogenic KRas suppresses inflammation-associated senescence of pancreatic ductal cells. | |
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MedLine Citation:
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PMID: 21075310 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mutational activation of KRas is the first and most frequently detected genetic lesion in pancreatic ductal adenocarcinoma (PDAC). However, the precise role of oncogenic KRas in the pathogenesis of PDAC is not fully understood. Here, we report that the endogenous expression of oncogenic KRas suppresses premature senescence in primary pancreatic duct epithelial cells (PDEC). Oncogenic KRas-mediated senescence bypass is conferred by the upregulation of the basic helix-loop-helix transcription factor Twist that in turn abrogates p16(INK4A) induction. Moreover, the KRas-Twist-p16(INK4A) senescence bypass pathway is employed in vivo to prevent inflammation-associated senescence of pancreatic ductal epithelium. Our findings indicate that oncogenic KRas could contribute to PDAC initiation by protecting cells from entering a state of permanent growth arrest. |
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Authors:
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Kyoung Eun Lee; Dafna Bar-Sagi |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Cancer cell Volume: 18 ISSN: 1878-3686 ISO Abbreviation: Cancer Cell Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-15 Completed Date: 2010-12-16 Revised Date: 2012-09-20 |
Medline Journal Info:
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Nlm Unique ID: 101130617 Medline TA: Cancer Cell Country: United States |
Other Details:
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Languages: eng Pagination: 448-58 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Cell and Molecular Biology Program, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carcinoma, Pancreatic Ductal / genetics* Cell Aging / genetics* Cell Proliferation Cells, Cultured Cyclin-Dependent Kinase Inhibitor p16 / genetics, metabolism Mice Nuclear Proteins / genetics, metabolism Pancreatic Ducts / cytology* Pancreatic Neoplasms / genetics* Pancreatitis / metabolism Proto-Oncogene Proteins p21(ras) / genetics, metabolism, physiology* RNA, Messenger / metabolism Tumor Suppressor Protein p53 / genetics, metabolism Twist Transcription Factor / genetics, metabolism beta-Galactosidase / analysis |
| Grant Support | |
ID/Acronym/Agency:
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CA055360/CA/NCI NIH HHS; R01 CA055360/CA/NCI NIH HHS; R56 CA055360/CA/NCI NIH HHS; R56 CA055360-19/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclin-Dependent Kinase Inhibitor p16; 0/Nuclear Proteins; 0/RNA, Messenger; 0/Tumor Suppressor Protein p53; 0/Twist Transcription Factor; 136253-27-5/Twist1 protein, mouse; EC 3.2.1.23/beta-Galactosidase; EC 3.6.5.2/Kras2 protein, mouse; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras) |
| Comments/Corrections | |
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