| The role of mRNA stability and transcription in O6-methylguanine DNA methyltransferase (MGMT) expression in Mer+ human tumor cells. | |
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MedLine Citation:
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PMID: 7554086 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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R A Kroes; L C Erickson |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Carcinogenesis Volume: 16 ISSN: 0143-3334 ISO Abbreviation: Carcinogenesis Publication Date: 1995 Sep |
Date Detail:
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Created Date: 1995-11-20 Completed Date: 1995-11-20 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 2255-7 Citation Subset: IM |
Affiliation:
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Department of Medicine, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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CA45628/CA/NCI NIH HHS; CA57725/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; EC 2.1.1.-/Methyltransferases; EC 2.1.1.63/O(6)-Methylguanine-DNA Methyltransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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