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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2004-5-11
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pubmed:abstractText |
The increased levels of c-Myc protein observed previously in an ovarian carcinoma cell line stably transfected to express HER2 has suggested a role for the HER2 pathway in c-Myc expression. Analysis of HER2-transfected cells stimulated with heregulin beta1 (HRG) revealed increased c-Myc protein levels but not a corresponding increase in c-Myc mRNA expression or any change in c-Myc protein half-life. Transfection of HER2-overexpressing cells with a construct containing the 5' untranslated region (5'UTR) of c-Myc mRNA originated from the P2 promoter and placed upstream of the Renilla luciferase gene, enhanced reporter expression upon stimulation with HRG. The HRG-mediated increase in reporter activity correlated with the HRG-mediated induction observed for c-Myc protein, identifying the P2-derived leader (P2L) of c-Myc mRNA as the cis-element involved in c-Myc translational induction. Both the increase in c-Myc protein levels and P2L-enhanced translational activity were inhibited by the PI3K inhibitor wortmannin. Together, these results demonstrate that HRG stimulation of HER2 overexpressing cells leads to enhanced c-Myc protein synthesis through activation of the PI3K/Akt/mTOR pathway and that the P2L of c-Myc mRNA is the element responsible for induction of c-Myc translation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Androstadienes,
http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/Dactinomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/MTOR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Neuregulin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/heregulin beta1,
http://linkedlifedata.com/resource/pubmed/chemical/wortmannin
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9541
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2004 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:volume |
200
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
82-8
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15137060-5' Untranslated Regions,
pubmed-meshheading:15137060-Androstadienes,
pubmed-meshheading:15137060-Carcinoma,
pubmed-meshheading:15137060-Cell Line, Tumor,
pubmed-meshheading:15137060-Clone Cells,
pubmed-meshheading:15137060-Cycloheximide,
pubmed-meshheading:15137060-Dactinomycin,
pubmed-meshheading:15137060-Enzyme Inhibitors,
pubmed-meshheading:15137060-Female,
pubmed-meshheading:15137060-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:15137060-Genes, Reporter,
pubmed-meshheading:15137060-Genes, erbB-2,
pubmed-meshheading:15137060-Genes, myc,
pubmed-meshheading:15137060-Humans,
pubmed-meshheading:15137060-Luciferases,
pubmed-meshheading:15137060-Neuregulin-1,
pubmed-meshheading:15137060-Ovarian Neoplasms,
pubmed-meshheading:15137060-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:15137060-Promoter Regions, Genetic,
pubmed-meshheading:15137060-Protein Biosynthesis,
pubmed-meshheading:15137060-Protein Kinases,
pubmed-meshheading:15137060-Protein Synthesis Inhibitors,
pubmed-meshheading:15137060-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15137060-Proto-Oncogene Proteins,
pubmed-meshheading:15137060-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15137060-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:15137060-RNA, Messenger,
pubmed-meshheading:15137060-Signal Transduction,
pubmed-meshheading:15137060-TOR Serine-Threonine Kinases
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pubmed:year |
2004
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pubmed:articleTitle |
HER2 signaling enhances 5'UTR-mediated translation of c-Myc mRNA.
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pubmed:affiliation |
Molecular Targeting Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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