Document Detail

Okadaic acid stimulates osteopontin expression through de novo induction of AP-1.
MedLine Citation:
PMID:  12210726     Owner:  NLM     Status:  MEDLINE    
Osteopontin, a major non-collagenous bone matrix protein, is strikingly upregulated in various tissues under certain pathologic conditions, including cancer. However, the mechanism of upregulation of the osteopontin gene in tumor cells remains unclear. Okadaic acid, a strong non-phorbol ester tumor promoter, is known to stimulate the expression of osteopontin. The aim of the present study was to understand the mechanism by which okadaic acid regulates osteopontin gene expression. Okadaic acid stimulated osteopontin mRNA expression in several cell lines within 3 h, and the increase in osteopontin mRNA was sustained for 24 h. New protein synthesis was required for the okadaic acid-elicited increase in osteopontin mRNA expression. A serial promoter deletion study showed that the okadaic acid-response element is located between positions -265 and -73, a sequence that includes the Runx2, Ets-1, and AP-1 binding sequences. Okadaic acid increased the mRNA expression of AP-1 components but not of Runx2 or Ets-1. Site-directed mutagenesis and electrophoretic mobility shift assays confirmed that protein binding of the AP-1 consensus sequence is necessary for the okadaic acid-mediated osteopontin gene upregulation. These results indicate that de novo induction of the oncoprotein AP-1 is required for okadaic acid-stimulated osteopontin gene upregulation.
Hyun-Jung Kim; Mi-Hye Lee; Hyun-Jung Kim; Hong-In Shin; Je-Yong Choi; Hyun-Mo Ryoo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  87     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2002  
Date Detail:
Created Date:  2002-12-18     Completed Date:  2003-04-15     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  93-102     Citation Subset:  IM    
Department of Biochemistry, School of Dentistry, Kyungpook National University, 101 Dong, In-dong, Jung-gu, Daegu, 700-422, Korea.
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MeSH Terms
3T3 Cells
Binding Sites
Blotting, Northern
Cell Nucleus / metabolism
Enzyme Inhibitors / pharmacology*
Gene Deletion
Genes, Reporter
Luciferases / metabolism
Mice, Inbred C3H
Mutagenesis, Site-Directed
Okadaic Acid / pharmacology*
Osteoblasts / metabolism
Plasmids / metabolism
Promoter Regions, Genetic
Protein Binding
Proto-Oncogene Protein c-ets-1
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-ets
RNA, Messenger / metabolism
Reactive Oxygen Species
Sialoglycoproteins / biosynthesis*,  metabolism
Time Factors
Transcription Factor AP-1 / metabolism*
Transcription Factors / metabolism
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Ets1 protein, mouse; 0/Proto-Oncogene Protein c-ets-1; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-ets; 0/RNA, Messenger; 0/Reactive Oxygen Species; 0/Sialoglycoproteins; 0/Spp1 protein, mouse; 0/Transcription Factor AP-1; 0/Transcription Factors; 106441-73-0/Osteopontin; 78111-17-8/Okadaic Acid; EC 1.13.12.-/Luciferases

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

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