Document Detail


Amplification of DNA sequences coding for the Na,K-ATPase alpha-subunit in ouabain-resistant C+ cells.
MedLine Citation:
PMID:  3023935     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have studied the mechanism of cellular resistance to cardiac glycosides in C+ cells. C+ cells were resistant to ouabain and overproduced plasma membrane-bound Na,K-ATPase relative to parental HeLa cells. Overexpression of Na,K-ATPase in C+ cells correlated with increased ATPase mRNA levels and amplification (approximately 100 times) of the ATPase gene. Growth of C+ cells in ouabain-free medium resulted in a marked decline in ATPase mRNA and DNA levels. However, when cells were reexposed to ouabain, they proliferated and ATPase mRNA and DNA sequences were reamplified. Restriction analysis of C+ and other human DNA samples revealed the occurrence of rearrangements in the region of the Na,K-ATPase gene in C+ cells. Furthermore, C+ cells expressed an ATPase mRNA species not found in HeLa cells. These results suggest that amplification of the gene coding for Na,K-ATPase results in overproduction of Na,K-ATPase polypeptides. Amplification of the ATPase gene or the expression of new ATPase mRNA sequences or both may also be responsible for acquisition of the ouabain-resistant phenotype.
Authors:
J R Emanuel; S Garetz; J Schneider; J F Ash; E J Benz; R Levenson
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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:  Molecular and cellular biology     Volume:  6     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1986 Jul 
Date Detail:
Created Date:  1987-01-20     Completed Date:  1987-01-20     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2476-81     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Cells, Cultured
DNA / analysis*
Drug Resistance
Gene Amplification*
Gene Expression Regulation
Hela Cells / enzymology
Humans
Ouabain / pharmacology*
RNA, Messenger / metabolism
Sodium-Potassium-Exchanging ATPase / genetics*
Grant Support
ID/Acronym/Agency:
CA-38992/CA/NCI NIH HHS; HL-01098/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 630-60-4/Ouabain; 9007-49-2/DNA; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase
Comments/Corrections

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