Matches in SemOpenAlex for { <https://semopenalex.org/work/W1415593923> ?p ?o ?g. }
- W1415593923 endingPage "193" @default.
- W1415593923 startingPage "185" @default.
- W1415593923 abstract "The DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) confers therapeutic resistance to DNA alkylating agents, including temozolomide. It is largely believed that MGMT promoter methylation is associated with down regulation of MGMT transcription and corresponding protein expression, thereby predisposing tumor cells to the toxic effect of temozolomide. Here we rigorously examined this underlying assumption.We examined the correlation between MGMT promoter methylation, transcription, and protein expression using The Cancer Genome Atlas (TCGA) glioblastoma database as well as an independent collection of glioblastoma specimens.In both analyses, we found that MGMT promoter methylation status correlates well with low MGMT mRNA levels (p = 0.04). On the other hand, glioblastomas with unmethylated MGMT promoters exhibited a wide range of MGMT mRNA expression. Intriguingly, the MGMT mRNA levels correlated poorly with MGMT protein levels by Western blotting (R(2) = 0.04, p = 0.34) or by ImmunoHistoChemical (IHC) stain quantitation (R(2) = 0.02, p = 0.50). To exclude the possibility that the poor correlation was due to substandard specimens, we determined the mRNA and protein levels of Colony Stimulating Factor 1 (CSF1), a gene previously shown to exhibit excellent mRNA/protein correlation. In contrast to MGMT, the mRNA level of CSF1 correlated well with the protein level (R(2) = 0.47, p = 0.001). Importantly, long-term passaged glioblastoma cell lines with comparable MGMT transcript levels differed in MGMT protein levels, suggesting mechanisms of post-transcriptional regulation. Accordingly, the correlation between MGMT promoter methylation and MGMT protein expression was poor (p = 0.27). In silico analysis predicted potential binding sites for several miRNA within the 3'UTR of MGMT, suggesting a mechanism for the post-transcriptional of MGMT.Our results suggest mechanisms such as miRNA mediated regulation for post-transcriptional regulation of MGMT. Identification of these mechanisms should enhance the value of MGMT based prognostic or predictive biomarker strategies." @default.
- W1415593923 created "2016-06-24" @default.
- W1415593923 creator A5001031272 @default.
- W1415593923 creator A5005526815 @default.
- W1415593923 creator A5013266511 @default.
- W1415593923 creator A5022662736 @default.
- W1415593923 creator A5027695659 @default.
- W1415593923 creator A5028793885 @default.
- W1415593923 creator A5040257921 @default.
- W1415593923 creator A5072374777 @default.
- W1415593923 creator A5075442335 @default.
- W1415593923 creator A5075835176 @default.
- W1415593923 date "2012-05-25" @default.
- W1415593923 modified "2023-09-25" @default.
- W1415593923 title "Post-transcriptional regulation of O6-methylguanine-DNA methyltransferase MGMT in glioblastomas" @default.
- W1415593923 cites W1558094668 @default.
- W1415593923 cites W1598808071 @default.
- W1415593923 cites W1983274728 @default.
- W1415593923 cites W1985115576 @default.
- W1415593923 cites W1995740954 @default.
- W1415593923 cites W1999549596 @default.
- W1415593923 cites W2001443196 @default.
- W1415593923 cites W2035021866 @default.
- W1415593923 cites W2035599494 @default.
- W1415593923 cites W2044415369 @default.
- W1415593923 cites W2045830695 @default.
- W1415593923 cites W2053701783 @default.
- W1415593923 cites W2079203845 @default.
- W1415593923 cites W2088404098 @default.
- W1415593923 cites W2097155839 @default.
- W1415593923 cites W2098548617 @default.
- W1415593923 cites W2112592259 @default.
- W1415593923 cites W2113012900 @default.
- W1415593923 cites W2121893446 @default.
- W1415593923 cites W2123079914 @default.
- W1415593923 cites W2123321988 @default.
- W1415593923 cites W2131981377 @default.
- W1415593923 cites W2137868544 @default.
- W1415593923 cites W2149564446 @default.
- W1415593923 cites W2155755884 @default.
- W1415593923 cites W2158565915 @default.
- W1415593923 cites W2158681922 @default.
- W1415593923 cites W2328946792 @default.
- W1415593923 cites W958327846 @default.
- W1415593923 doi "https://doi.org/10.3233/cbm-2012-0245" @default.
- W1415593923 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22674304" @default.
- W1415593923 hasPublicationYear "2012" @default.
- W1415593923 type Work @default.
- W1415593923 sameAs 1415593923 @default.
- W1415593923 citedByCount "33" @default.
- W1415593923 countsByYear W14155939232013 @default.
- W1415593923 countsByYear W14155939232014 @default.
- W1415593923 countsByYear W14155939232015 @default.
- W1415593923 countsByYear W14155939232016 @default.
- W1415593923 countsByYear W14155939232017 @default.
- W1415593923 countsByYear W14155939232018 @default.
- W1415593923 countsByYear W14155939232019 @default.
- W1415593923 countsByYear W14155939232020 @default.
- W1415593923 countsByYear W14155939232021 @default.
- W1415593923 countsByYear W14155939232022 @default.
- W1415593923 countsByYear W14155939232023 @default.
- W1415593923 crossrefType "journal-article" @default.
- W1415593923 hasAuthorship W1415593923A5001031272 @default.
- W1415593923 hasAuthorship W1415593923A5005526815 @default.
- W1415593923 hasAuthorship W1415593923A5013266511 @default.
- W1415593923 hasAuthorship W1415593923A5022662736 @default.
- W1415593923 hasAuthorship W1415593923A5027695659 @default.
- W1415593923 hasAuthorship W1415593923A5028793885 @default.
- W1415593923 hasAuthorship W1415593923A5040257921 @default.
- W1415593923 hasAuthorship W1415593923A5072374777 @default.
- W1415593923 hasAuthorship W1415593923A5075442335 @default.
- W1415593923 hasAuthorship W1415593923A5075835176 @default.
- W1415593923 hasConcept C101762097 @default.
- W1415593923 hasConcept C104317684 @default.
- W1415593923 hasConcept C105580179 @default.
- W1415593923 hasConcept C134935766 @default.
- W1415593923 hasConcept C138885662 @default.
- W1415593923 hasConcept C150194340 @default.
- W1415593923 hasConcept C153911025 @default.
- W1415593923 hasConcept C179926584 @default.
- W1415593923 hasConcept C190727270 @default.
- W1415593923 hasConcept C2777389519 @default.
- W1415593923 hasConcept C2778227246 @default.
- W1415593923 hasConcept C2779527866 @default.
- W1415593923 hasConcept C2779979206 @default.
- W1415593923 hasConcept C33288867 @default.
- W1415593923 hasConcept C41895202 @default.
- W1415593923 hasConcept C502942594 @default.
- W1415593923 hasConcept C54355233 @default.
- W1415593923 hasConcept C86803240 @default.
- W1415593923 hasConcept C91965660 @default.
- W1415593923 hasConceptScore W1415593923C101762097 @default.
- W1415593923 hasConceptScore W1415593923C104317684 @default.
- W1415593923 hasConceptScore W1415593923C105580179 @default.
- W1415593923 hasConceptScore W1415593923C134935766 @default.
- W1415593923 hasConceptScore W1415593923C138885662 @default.
- W1415593923 hasConceptScore W1415593923C150194340 @default.
- W1415593923 hasConceptScore W1415593923C153911025 @default.