Document Detail


Up-regulation of glutathione biosynthesis in NIH3T3 cells transformed with the ETV6-NTRK3 gene fusion.
MedLine Citation:
PMID:  15750350     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The ETV6-NTRK3 gene fusion, first identified in the chromosomal translocation in congenital fibrosarcoma, encodes a chimeric protein tyrosine kinase with potent transforming activity. ETV6-NTRK3-dependent transformation involves the joint action of NTRK3 signaling pathways, and aberrant cell cycle progression resulting from activation of Mek1 and Akt. The level of glutathione (GSH) was found to be markedly increased in ETV6-NTRK3-transformed NIH3T3 cells. The activities of the two GSH biosynthetic enzymes as well as of glutathione peroxidase, together with their mRNAs, were also higher in the transformed cells. The transformed cells were able to grow in the presence of GSH-depleting agents, whereas the control cells were not. L-Buthionine-(S,R)-sulfoximine (BSO) inhibited activation of Mek1 and Akt in the transformed NIH3T3 cells. These observations imply that up-regulation of GSH biosynthesis plays a central role in ETV6-NTRK3-induced transformation.
Authors:
Su-Jung Kim; Hong-Gyum Kim; Hye-Won Lim; Eun-Hee Park; Chang-Jin Lim
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecules and cells     Volume:  19     ISSN:  1016-8478     ISO Abbreviation:  Mol. Cells     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-03-07     Completed Date:  2005-07-28     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9610936     Medline TA:  Mol Cells     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  131-6     Citation Subset:  IM    
Affiliation:
Division of Life Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 200-701, Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Artificial Gene Fusion*
Buthionine Sulfoximine / pharmacology
Cell Transformation, Viral*
DNA-Binding Proteins / genetics*
Fibrosarcoma / congenital,  metabolism
Glutamate-Cysteine Ligase / metabolism
Glutathione / biosynthesis*
Glutathione Peroxidase / metabolism
Glutathione Synthase / metabolism
Maleates / pharmacology
Mice
NIH 3T3 Cells
Nuclear Proteins / genetics*
Proto-Oncogene Proteins c-ets
Receptor, trkC / genetics*
Repressor Proteins / genetics*
Translocation, Genetic
Up-Regulation*
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/ETS translocation variant 6 protein; 0/Maleates; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins c-ets; 0/Repressor Proteins; 141-05-9/diethyl maleate; 5072-26-4/Buthionine Sulfoximine; 70-18-8/Glutathione; EC 1.11.1.9/Glutathione Peroxidase; EC 2.7.10.1/Receptor, trkC; EC 6.3.2.2/Glutamate-Cysteine Ligase; EC 6.3.2.3/Glutathione Synthase

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