Document Detail


Increased c-jun/AP-1 levels in etoposide-resistant human leukemia K562 cells.
MedLine Citation:
PMID:  8068039     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
C-jun mRNA and AP-1 levels were examined in etoposide (VP-16)-sensitive (K562) and -resistant (K/VP.5) human leukemia cell lines. Previously, we reported that K/VP.5 cells have increased basal levels of mRNA for the protooncogene c-jun (Ritke MK and Yalowich JC, Biochem Pharmacol 46: 2007-2020, 1993). In this study, we show that the 3-fold increase in c-jun transcripts in K/VP.5 cells was accompanied by a 2-fold increase in the stability of the mRNA for this gene and a nearly 2-fold increase in AP-1 DNA binding activity compared with parental K562 cells. Treatment of K562 and K/VP.5 cells with 50-200 microM VP-16 resulted in 3- to 10-fold stimulation of c-jun transcripts, which peaked 90-150 min after addition of drug and remained elevated up to 5 hr. In contrast, amsacrine stimulated the levels of c-jun mRNA only 3-fold in both cell lines, and its c-jun stimulatory effects were decreased at concentrations greater than 50 microM. VP-16 stimulation of c-jun mRNA levels resulted in a 2-fold increase in AP-1 binding activity in K562 but not in K/VP.5 cells. Taken together, these results suggest that posttranscriptional changes in c-jun mRNA regulation may be associated with acquired resistance to VP-16.
Authors:
M K Ritke; V V Bergoltz; W P Allan; J C Yalowich
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  48     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  1994 Aug 
Date Detail:
Created Date:  1994-09-20     Completed Date:  1994-09-20     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  525-33     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, University of Pittsburgh School of Medicine, PA 15261.
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MeSH Terms
Descriptor/Qualifier:
DNA Topoisomerases, Type II / antagonists & inhibitors,  genetics
Drug Resistance
Etoposide / pharmacology*
Genes, jun*
Humans
Proto-Oncogene Proteins c-jun / analysis*,  genetics
RNA, Messenger / analysis
Transcription, Genetic
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
CA-51657/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-jun; 0/RNA, Messenger; 33419-42-0/Etoposide; EC 5.99.1.3/DNA Topoisomerases, Type II

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