Induction of the DNA repair gene O6-methylguanine—DNA methyltransferase by dexamethasone in glioblastomas

Ueda, Shigeo; Mineta, Toshihiro; Nakahara, Yukiko; Okamoto, Hiroaki; Shiraishi, Tetsuya; Tabuchi, Kazuo

doi:10.3171/jns.2004.101.4.0659

Cited by 44 publications

(26 citation statements)

References 16 publications

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“…In addition, MGMT expression can be regulated by TFs acting as transcriptional activators or repressors [12,36]. Although most studies addressing MGMT expression have so far focused on epigenetic mechanisms, TFs such as AP-1 [40], Sp1 [41], NF-κB [42], HIF-1α [36,43], GRE [44] and the CBP-p300 transcriptional coactivator complex [45], have also been reported to be able to up-regulate MGMT expression by enhancing the MGMT promoter activity [12,36]. On the other hand, p53 [46] and IFN-β [47] have been reported to be able to down-regulate MGMT expression.…”

Section: Discussionmentioning

confidence: 99%

MGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression

Cross

Speidel

et al. 2016

Cell Oncol.

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Section: Discussionmentioning

confidence: 99%

MGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression

Cross

Speidel

et al. 2016

Cell Oncol.

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“…We first tested the effects of TMZ on U87-MG, U251, A172, and BT325 glioma cell lines, and found that U251, A172, and BT325 cell lines was not sensitive to TMZ. Methylation of MGMT promoter has been indicated as a common marker for predicting chemotherapy and prognosis of TMZ on glioma patient [19-21]. Consistently, U251, A172, and BT325 have unmethylated MGMT promoter, which rend them to TMZ resistance.…”

Section: Discussionmentioning

confidence: 99%

Chemotherapeutic effect of tamoxifen on temozolomide-resistant gliomas

Liu

Yang

et al. 2015

Anti-Cancer Drugs

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Tamoxifen, a selective estrogen receptor modulator, is widely used in chemotherapy of estrogen receptor-positive breast cancer. Recent studies have indicated that tamoxifen might have potential chemotherapeutic effect on glioma. In the present study, we determined the chemotherapeutic action of tamoxifen on human glioma cell lines. Methylation of 06-methylguanine-DNA methyltransferase expression was identified in A172, U251 and BT325 glioma cell lines, but not U87 cell line. Consistently, A172, U251 and BT325 cell lines are resistant to temozolomide. Tamoxifen induced significant cytotoxic action in A172, U251, BT325, and U87 cell lines. Further Hoechst 33342 staining and apoptosis flow cytometric analysis demonstrated that tamoxifen induced apoptosis in BT325 cell line. Mitochondrial complex analysis indicated that tamoxifen, but not other estrogen receptor modulators, dose dependently inhibit complex I activity. In summary, our study suggests that tamoxifen might have chemotherapeutic effect on temozolomide resistant glioma through its direct action on mitochondrial complex I inhibition and could provide further evidence to support future clinical trial of tamoxifen for the treatment of glioblastoma.

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“…18) A recent experimental study has demonstrated that the induction of MGMT by dexamethasone was associated with increased resistance to ACNU in glioma cells. 22) Conversely, IFN-b down-regulates the expression of MGMT, enhancing chemotoxicity against glioma cells. 15) Therefore, the real responsiveness to adjuvant chemotherapy might be masked by these therapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

Preliminary Individualized Chemotherapy for Malignant Astrocytomas Based on O6-Methylguanine-Deoxyribonucleic Acid Methyltransferase Methylation Analysis

Watanabe

Katayama

Ogino

et al. 2006

Neurol. Med. Chir.(Tokyo)

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O 6 -methylguanine-deoxyribonucleic acid methyltransferase gene (MGMT) methylation is apparently correlated with responsiveness to nitrosourea chemotherapy, suggesting this alkylating agent should be effective against MGMT-methylated tumors. MGMT appears not to be linked to platinum resistance, so platinum chemotherapy should be used for MGMT-unmethylated tumors. This study was a preliminary trial of individualized chemotherapy based on MGMT methylation status in a total of 20 patients with newly diagnosed malignant astrocytomas (9 anaplastic astrocytomas and 11 glioblastomas multiforme). The procarbazine, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-2(2-chloroethyl)-3-nitrosourea, and vincristine (PAV) regimen was administered to seven patients with MGMT-methylated tumors, and the carboplatin and etoposide (CE) regimen was administered to 13 patients with MGMT-unmethylated tumors. Objective response to the PAV therapy was noted in all three patients with measurable residual tumor (2 complete responses and 1 partial response). Five of the seven patients continued to be diseasefree after initiation of the PAV therapy. Objective response to the CE therapy was seen in only one of seven patients with measurable residual tumor (1 partial response). Three of the 13 patients were free from progression, whereas the remaining 10 patients showed early progression. The PAV regimen is effective against MGMT-methylated malignant astrocytomas, but the CE regimen is not useful at the given dose and schedule in MGMT-unmethylated tumors.

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Induction of the DNA repair gene O6-methylguanine—DNA methyltransferase by dexamethasone in glioblastomas

Abstract: These results indicate that dexamethasone-mediated upregulation of MGMT limits the efficiency of alkylating agents in the treatment of malignant gliomas.

Cited by 44 publications

References 16 publications

MGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression

MGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression

Chemotherapeutic effect of tamoxifen on temozolomide-resistant gliomas

Preliminary Individualized Chemotherapy for Malignant Astrocytomas Based on O6-Methylguanine-Deoxyribonucleic Acid Methyltransferase Methylation Analysis

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