Open Access

Regulation of expression of O6-methylguanine-DNA methyltransferase and the treatment of glioblastoma (Review)

  • Authors:
    • Giulio Cabrini
    • Enrica Fabbri
    • Cristiana Lo Nigro
    • Maria Cristina Dechecchi
    • Roberto Gambari
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  • Published online on: May 29, 2015     https://doi.org/10.3892/ijo.2015.3026
  • Pages: 417-428
  • Copyright: © Cabrini et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

O-6-methylguanine-DNA methyltransferase (MGMT) is an abundantly expressed nuclear protein dealkylating O6-methylguanine (O6-MG) DNA residue, thus correcting the mismatches of O6-MG with a thymine residue during DNA replication. The dealkylating effect of MGMT is relevant not only in repairing DNA mismatches produced by environmental alkylating agents promoting tumor pathogenesis, but also when alkylating molecules are applied in the chemotherapy of different cancers, including glioma, the most common primary tumor of the central nervous system. Elevated MGMT gene expression is known to confer resistance to the treatment with the alkylating drug temozolomide in patients affected by gliomas and, on the contrary, methylation of MGMT gene promoter, which causes reduction of MGMT protein expression, is known to predict a favourable response to temozolomide. Thus, detecting expression levels of MGMT gene is crucial to indicate the option of alkylating agents or to select patients directly for a second line targeted therapy. Further study is required to gain insights into MGMT expression regulation, that has attracted growing interest recently in MGMT promoter methylation, histone acetylation and microRNAs expression. The review will focus on the epigenetic regulation of MGMT gene, with translational applications to the identification of biomarkers predicting response to therapy and prognosis.
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August-2015
Volume 47 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Cabrini G, Fabbri E, Lo Nigro C, Dechecchi MC and Gambari R: Regulation of expression of O6-methylguanine-DNA methyltransferase and the treatment of glioblastoma (Review). Int J Oncol 47: 417-428, 2015.
APA
Cabrini, G., Fabbri, E., Lo Nigro, C., Dechecchi, M.C., & Gambari, R. (2015). Regulation of expression of O6-methylguanine-DNA methyltransferase and the treatment of glioblastoma (Review). International Journal of Oncology, 47, 417-428. https://doi.org/10.3892/ijo.2015.3026
MLA
Cabrini, G., Fabbri, E., Lo Nigro, C., Dechecchi, M. C., Gambari, R."Regulation of expression of O6-methylguanine-DNA methyltransferase and the treatment of glioblastoma (Review)". International Journal of Oncology 47.2 (2015): 417-428.
Chicago
Cabrini, G., Fabbri, E., Lo Nigro, C., Dechecchi, M. C., Gambari, R."Regulation of expression of O6-methylguanine-DNA methyltransferase and the treatment of glioblastoma (Review)". International Journal of Oncology 47, no. 2 (2015): 417-428. https://doi.org/10.3892/ijo.2015.3026