Document Detail


Posttranscriptional regulation of cyclooxygenase-2 in rat intestinal epithelial cells.
MedLine Citation:
PMID:  11228545     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Modulation of cyclooxygenase-2 (COX-2) mRNA stability plays an important role in the regulation of its expression by oncogenic Ras. Here, we evaluate COX-2 mRNA stability in response to treatment with two known endogenous promoters of gastrointestinal cancer, the bile acid (chenodeoxycholate; CD) and ceramide. Treatment with CD and ceramide resulted in a 10-fold increase in the level of COX-2 protein and a four-fold lengthening of the half-life of COX-2 mRNA. COX-2 mRNA stability was assessed by Northern blot analysis and by evaluating the AU-rich element located in the COX-2 3'-UTR. A known inhibitor of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK), PD98059, reversed the effects of CD or ceramide to stabilize COX-2 mRNA. Overexpression of a dominant-negative ERK-1 or ERK-2 protein also led to destabilization of COX-2 mRNA. Treatment with a p38 MAPK inhibitor, PD169316, or transfection with a dominant-negative p38 MAPK construct reversed the effect of CD or ceramide to stabilize COX-2 mRNA. Expression of a dominant-negative c-Jun N-terminal kinase (JNK) had no effect on COX-2 mRNA stability in cells treated with CD or ceramide. We conclude that posttranscriptional mechanisms play an important role in the regulation of COX-2 expression during carcinogenesis.
Authors:
Z Zhang; H Sheng; J Shao; R D Beauchamp; R N DuBois
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neoplasia (New York, N.Y.)     Volume:  2     ISSN:  1522-8002     ISO Abbreviation:  Neoplasia     Publication Date:    2000 Nov-Dec
Date Detail:
Created Date:  2001-03-06     Completed Date:  2002-04-01     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100886622     Medline TA:  Neoplasia     Country:  United States    
Other Details:
Languages:  eng     Pagination:  523-30     Citation Subset:  IM    
Affiliation:
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Ceramides / pharmacology
Chenodeoxycholic Acid / pharmacology
Cyclooxygenase 2
Gene Expression Regulation, Enzymologic*
Genes, Dominant
Intestinal Mucosa / drug effects*,  enzymology
Isoenzymes / genetics*,  metabolism
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase Kinases / metabolism
Mitogen-Activated Protein Kinases / metabolism
Prostaglandin-Endoperoxide Synthases / genetics*,  metabolism
RNA Processing, Post-Transcriptional / genetics*
RNA, Messenger / metabolism*
Rats
p38 Mitogen-Activated Protein Kinases
Grant Support
ID/Acronym/Agency:
CA69457/CA/NCI NIH HHS; DK47297/DK/NIDDK NIH HHS; DR52334//PHS HHS; P0 CA77839/CA/NCI NIH HHS; P01 CA77839/CA/NCI NIH HHS; P30 CA68485/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Ceramides; 0/Isoenzymes; 0/RNA, Messenger; 474-25-9/Chenodeoxycholic Acid; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases
Comments/Corrections

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