title: Impact of the DNA methyltransferases expression on the methylation status of apoptosis-associated genes in glioblastoma multiforme.
abstract: Disruption of apoptosis is considered as an important factor aiding tumorigenesis, and aberrant DNA methylation of apoptosis-associated genes could be an important and significant mechanism through which tumor cells avoid apoptosis. However, little is known about (1) the impact of methylation status of apoptosis-associated genes on the presence of apoptosis evasion phenotype in glioma; and (2) the molecular mechanism governing the aberrant methylation of apoptosis-associated genes in glioma. By analyzing human glioma biopsies, we first show that low level of apoptosis in tumor is correlated with aberrant methylation of the bcl-2, bax and XAF-1 genes, but not with the aberrant methylation of the bcl-w, survivin, TMS1, caspase-8 and HRK genes. Our work also indicates that the expression levels of DNA methyltransferase 1 (Dnmt1), Dnmt3b and Dnmt1/Dnmt3a coregulate the methylation status of survivin, TMS1 and caspase-8, whereas no correlation was observed between the expression level of Dnmts and the methylation status of the bcl-w, bcl-2, bax, XAF-1 and HRK genes. Thus, these results indicate that the epigenetic regulation of some apoptosis-regulated genes could dictate whether glioma harbors the apoptosis evasion phenotype, and provide some bases to the identification of the methylation machineries of apoptosis-associated genes for which the Dnmt expression acts as a limiting factor.
authors.affiliation: INSERM U892, Centre de Recherche en Cancérologie, Equipe Aspect mécanistiques et physiopathologiques de l'activité des proteines de la famille de Bcl-2 (Equipe labelisée Ligue Nationale Contre le Cancer), Nantes, France.
authors.forename: E
authors.initials: E
authors.lastname: Hervouet
authors.forename: F M
authors.initials: FM
authors.lastname: Vallette
authors.forename: P-F
authors.initials: PF
authors.lastname: Cartron
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D053181:Caspase 8 / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D000077022:Survivin; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C107489:BIRC5 protein, human; D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C402202:PYCARD protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; C417551:XAF1 protein, human; D051028:bcl-2-Associated X Protein; D004248:DNA (Cytosine-5-)-Methyltransferases; D053181:Caspase 8