Document Detail


The role of mRNA stability and transcription in O6-methylguanine DNA methyltransferase (MGMT) expression in Mer+ human tumor cells.
MedLine Citation:
PMID:  7554086     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have recently reported that following depletion of O6-methylguanine DNA methyltransferase (MGMT) activity by acute streptozotocin (STZ) treatment to sensitize innately chloroethylnitrosourea (CENU)-resistant HT-29 cells, the eventual repletion of activity occurs with no concommitant alterations in steady-state MGMT mRNA levels. This suggestion of a potentially stable transcript prompted studies to define the relative contributions of MGMT mRNA stability and transcription to cellular MGMT expression. Northern analysis of MGMT mRNA in actinomycin D-treated HT-29, MR-1 and A2182 cells, ranging in relative MGMT expression from high to low respectively, demonstrates relatively long MGMT mRNA half-lives of > 10-12 h. Cell lines with low and moderate levels of MGMT mRNA appear to have longer mRNA half-lives than those with high levels. Run-on transcription in nuclei isolated from cells with low to moderate MGMT mRNA levels demonstrates undetectable basal MGMT transcription rates. Collectively these data suggest that a very low transcription rate, coupled with a stable mRNA molecule, might result in the translation of pre-existing mRNA molecules. This translation may be responsible for the gradual recovery of MGMT and CENU resistance over 24 h following MGMT depletion.
Authors:
R A Kroes; L C Erickson
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Carcinogenesis     Volume:  16     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  1995 Sep 
Date Detail:
Created Date:  1995-11-20     Completed Date:  1995-11-20     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2255-7     Citation Subset:  IM    
Affiliation:
Department of Medicine, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
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MeSH Terms
Descriptor/Qualifier:
DNA Repair
Drug Stability
Gene Expression
HT29 Cells / enzymology*,  metabolism
Humans
Methylation
Methyltransferases / biosynthesis*,  genetics
O(6)-Methylguanine-DNA Methyltransferase
RNA, Messenger / genetics,  metabolism,  physiology*
Transcription, Genetic*
Grant Support
ID/Acronym/Agency:
CA45628/CA/NCI NIH HHS; CA57725/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; EC 2.1.1.-/Methyltransferases; EC 2.1.1.63/O(6)-Methylguanine-DNA Methyltransferase

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