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. 2013 Jul 18;2(3):545-73.
doi: 10.3390/cells2030545.

DNA methylation and apoptosis resistance in cancer cells

Eric Hervouet  1 , Mathilde Cheray  2 , François Marie Vallette  3 , Pierre-François Cartron  4
Affiliations

DNA methylation and apoptosis resistance in cancer cells

Eric Hervouet et al. Cells. .

Abstract

Apoptosis is a cell death programme primordial to cellular homeostasis efficiency. This normal cell suicide program is the result of the activation of a cascade of events in response to death stimuli. Apoptosis occurs in normal cells to maintain a balance between cell proliferation and cell death. A deregulation of this balance due to modifications in the apoptosic pathway leads to different human diseases including cancers. Apoptosis resistance is one of the most important hallmarks of cancer and some new therapeutical strategies focus on inducing cell death in cancer cells. Nevertheless, cancer cells are resistant to treatment inducing cell death because of different mechanisms, such as DNA mutations in gene coding for pro-apoptotic proteins, increased expression of anti-apoptotic proteins and/or pro-survival signals, or pro-apoptic gene silencing mediated by DNA hypermethylation. In this context, aberrant DNA methylation patterns, hypermethylation and hypomethylation of gene coding for proteins implicated in apoptotic pathways are possible causes of cancer cell resistance. This review highlights the role of DNA methylation of apoptosis-related genes in cancer cell resistance.

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Figures

Figure 1
Figure 1
Mechanism of apoptosis. Activation of initiators caspase 8 and 10 are mediated in response to extrinsic stimuli and apoptosis signaling is controlled by anti- and pro-apoptotic protein interactions.
Figure 2
Figure 2
Mechanisms of DNA hypermethylation and apoptosis-related genes inactivation (a) Inactivation of RASSF1A by Dnmt/P53 cooperation. (b) Inactivation of DAPK by the ternary complex Dnmt/RelB/DAXX. (c) Specific methylation of BAX leading to BAX ψ or BAX silencing.
Figure 3
Figure 3
DNA methylation and anti-apoptotic strategies (a) Effects of both DNA demethylating agents and pro-methylation, mediated by folate, on apoptosis-related genes and apoptosis. (b) Conflicting results of demethylated agents and specific strategies against targeted DNA methylation on apoptosis.
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References

    1. Kuribara R., Honda H., Matsui H., Shinjyo T., Inukai T., Sugita K., Nakazawa S., Hirai H., Ozawa K., Inaba T. Roles of Bim in apoptosis of normal and Bcr-Abl-expressing hematopoietic progenitors. Mol. Cell. Biol. 2004;24:6172–6183. - PMC - PubMed
    1. Hanahan D., Weinberg R.A. The hallmarks of cancer. Cell. 2000;100:57–70. - PubMed
    1. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16:6–21. doi: 10.1101/gad.947102. - DOI - PubMed
    1. Chen T., Ueda Y., Dodge J.E., Wang Z., Li E. Establishment and maintenance of genomic methylation patterns in mouse embryonic stem cells by Dnmt3a and Dnmt3b. Mol. Cell. Biol. 2003;23:5594–5605. doi: 10.1128/MCB.23.16.5594-5605.2003. - DOI - PMC - PubMed
    1. Gama-Sosa M.A., Slagel V.A., Trewyn R.W., Oxenhandler R., Kuo K.C., Gehrke C.W., Ehrlich M. The 5-methylcytosine content of DNA from human tumors. Nucleic Acids Res. 1983;11:6883–6894. doi: 10.1093/nar/11.19.6883. - DOI - PMC - PubMed

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