Document Detail


Oncogenic KRas suppresses inflammation-associated senescence of pancreatic ductal cells.
MedLine Citation:
PMID:  21075310     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Kyoung Eun Lee; Dafna Bar-Sagi
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cancer cell     Volume:  18     ISSN:  1878-3686     ISO Abbreviation:  Cancer Cell     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-15     Completed Date:  2010-12-16     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101130617     Medline TA:  Cancer Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  448-58     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Cell and Molecular Biology Program, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
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:
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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