Document Detail


The role of p21(CIP1/WAF1) in growth of epithelial cells exposed to hyperoxia.
MedLine Citation:
PMID:  11238001     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previous studies have shown that hyperoxia inhibits proliferation and increases the expression of the tumor suppressor p53 and its downstream target, the cyclin-dependent kinase inhibitor p21(CIP1/WAF1), which inhibits proliferation in the G1 phase of the cell cycle. To determine whether growth arrest was mediated through activation of the p21-dependent G1 checkpoint, the kinetics of cell cycle movement during exposure to 95% O2 were assessed in the Mv1Lu and A549 pulmonary adenocarcinoma cell lines. Cell counts, 5-bromo-2'-deoxyuridine incorporation, and cell cycle analyses revealed that growth arrest of both cell lines occurred in S phase, with A549 cells also showing evidence of a G1 arrest. Hyperoxia increased p21 in A549 but not in Mv1Lu cells, consistent with the activation of the p21-dependent G1 checkpoint. The ability of p21 to exert the G1 arrest was confirmed by showing that hyperoxia inhibited proliferation of HCT 116 colon carcinoma cells predominantly in G1, whereas an isogenic line lacking p21 arrested in S phase. The cell cycle arrest in S phase appears to be a p21-independent process caused by a gradual reduction in the rate of DNA strand elongation. Our data reveal that hyperoxia inhibits proliferation in G1 and S phase and demonstrate that p53 and p21 retain their ability to affect G1 checkpoint control during exposure to elevated O2 levels.
Authors:
R C Rancourt; P C Keng; C E Helt; M A O'Reilly
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  280     ISSN:  1040-0605     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-03-12     Completed Date:  2001-04-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L617-26     Citation Subset:  IM    
Affiliation:
Department of Environmental Medicine, University of Rochester, Rochester, NY 14642, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Cell Division / physiology
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / metabolism,  physiology*
DNA / genetics
Epithelial Cells / metabolism,  pathology,  physiology
G1 Phase / physiology,  radiation effects
Gamma Rays
Hyperoxia / genetics,  metabolism,  pathology*,  physiopathology*
Phosphorylation
Transcription, Genetic
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / metabolism
Grant Support
ID/Acronym/Agency:
CA-73725/CA/NCI NIH HHS; ES-07026/ES/NIEHS NIH HHS; HL-58774/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Tumor Suppressor Protein p53; 56-65-5/Adenosine Triphosphate; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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