Source:http://linkedlifedata.com/resource/pubmed/id/10692471
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
2000-4-3
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pubmed:abstractText |
Oncogenic ras induces the expression of cyclooxygenase-2 (COX-2) in a variety of cells. Here we investigated the role of transforming growth factor-beta (TGF-beta) in the Ras-mediated induction of COX-2 in intestinal epithelial cells (RIE-1). RIE-1 cells were transfected with an inducible Ha-Ras(Val12) cDNA and are referred as RIE-iRas cells. the addition of 5 mM isopropyl-1-thio-beta-D-galactopyranoside (IPTG) induced the expression of Ha-Ras(Val12), closely followed by an increase in the expression of COX-2. Neutralizing anti-TGF-beta antibody partially blocked the Ras-induced increase in COX-2. Combined treatment with IPTG and TGF-beta1 resulted in a 20-50-fold increase in the levels of COX-2 mRNA. The t1/2 of COX-2 mRNA was increased from 13 to 24 min by Ha-Ras induction alone. The addition of TGF-beta1 further stabilized the COX-2 mRNA (t1/2 > 50 min). Stable transfection of a luciferase reporter construct containing the COX-2 3'-untranslated region (3'-UTR) revealed that TGF-beta1 treatment and Ras induction each stabilized the COX-2 3'-UTR. Combined treatment with IPTG and TGF-beta1 synergistically increased the luciferase activity. Furthermore, a conserved AU-rich region located in the proximal COX-2 3'-UTR is required for maximal stabilization of COX-2 3'-UTR by Ras or TGF-beta1 and is necessary for the synergistic stabilization of COX-2 3'-UTR by oncogenic Ras and TGF-beta1.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Isopropyl Thiogalactoside,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6628-35
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:10692471-3' Untranslated Regions,
pubmed-meshheading:10692471-Animals,
pubmed-meshheading:10692471-Cell Line,
pubmed-meshheading:10692471-Cyclooxygenase 2,
pubmed-meshheading:10692471-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:10692471-Genes, Reporter,
pubmed-meshheading:10692471-Intestines,
pubmed-meshheading:10692471-Isoenzymes,
pubmed-meshheading:10692471-Isopropyl Thiogalactoside,
pubmed-meshheading:10692471-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:10692471-RNA, Messenger,
pubmed-meshheading:10692471-Transfection,
pubmed-meshheading:10692471-Transforming Growth Factor beta,
pubmed-meshheading:10692471-ras Proteins
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pubmed:year |
2000
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pubmed:articleTitle |
Transforming growth factor-beta1 enhances Ha-ras-induced expression of cyclooxygenase-2 in intestinal epithelial cells via stabilization of mRNA.
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pubmed:affiliation |
Department of Surgery, The Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. hongmiao.sheng@mcmail.vanderbilt.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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