Decitabine (5-Aza-2′-deoxycytidine) decreased DNA methylation and expression of MDR-1 gene in K562/ADM cells

Ando, Takafumi; Nishimura, Manabu; Oka, Yoshitomo

doi:10.1038/sj.leu.2401914

Cited by 48 publications

(31 citation statements)

References 21 publications

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“…The MDR1 gene, for instance, has been paradoxically downregulated by DNA methylation inhibitors. This occurs via demethylation of a promoter region at the repressor site (minus 110 GC-box) of the MDR-1 gene in K562/ADM resistant cells [92].…”

Section: Pharmacoepigenetics Of Ribonucleotide Reductasementioning

confidence: 99%

Pharmacogenetics and pharmacoepigenetics of gemcitabine

et al. 2009

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Gemcitabine (2',2'-difluoro 2'deoxycytidine, dFdC) is an analog of cytosine with distinctive pharmacological properties and a wide antitumor-activity spectrum. The pharmacological characteristics of gemcitabine are unique because two main classes of genes are essential for its antitumor effects: membrane transporter protein-coding genes, whose products are responsible for drug intracellular uptake, as well as enzyme-coding genes, which catalyze its activation and inactivation. The study of the pharmacogenetics and pharmacoepigenetics of these two gene classes is greatly required to optimize the drug's therapeutic use in cancer. This review aims to provide an update of genetic and epigenetic bases that may account for interindividual variation in therapeutic outcome exhibited by gemcitabine.

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Section: Pharmacoepigenetics Of Ribonucleotide Reductasementioning

confidence: 99%

Pharmacogenetics and pharmacoepigenetics of gemcitabine

et al. 2009

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“…However, HRM has not yet been used to evaluate the percentage of methylation in this gene and the association of methylation percentage with gene expression. A previous study indicated that in K562 cells the ABCB1 promoter region had lowly methylated or unmethylated DNA and that ABCB1 gene expression was correlated to its methylation status (Ando et al, 2000). Additionally, DLD-1 cells also showed a correlation between the status of ABCB1 gene methylation and gene expression (Kim et al, 2009).…”

Section: Discussionmentioning

confidence: 97%

“…Several studies have revealed the presence of CpG islands from the first intron of ABCB1 to a few nucleotides upstream of the transcription start site (Nakayama et al, 1998). These DNA regions have been reported as targets of methylation (Jin and Scotto, 1998;Ando et al, 2000). Although a few studies have addressed the association between ABCB1 methylation status and the expression of this gene, the precise mechanism of ABCB1 gene expression regulation is not yet clear (Kantharidis et al, 1997;Nakayama et al, 1998;Toyota et al, 2001;Backer et al, 2005;Kim et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Accurate monitoring of promoter gene methylation with high-resolution melting polymerase chain reaction using the ABCB1 gene as a model

Mencalha¹,

Rodrigues²,

Abdelhay³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Multidrug resistance is the major cause of cancer chemotherapy failure. This phenotype is mainly due to the overexpression of the human ABCB1 gene. Several studies have shown that the transcriptional regulation of this gene is complex. Yet, the impact of this transcriptional regulation has not been well studied in a clinical setting. The acquired expression of ABCB1 is associated with the genomic instability of cancer cells. This includes the occurrence of mutational events that alter chromatin structures through epigenetic modifications such as promoter methylation. Therefore, it is important to introduce new clinical methods to monitor the methylation status of ABCB1 and determine its association with gene expression in order to be able to predict response to therapies. The high-resolution melting (HRM) method has emerged as a highly accurate and sensitive ABCB1 gene methylation analyses method to quantify methylation status at specific sites of DNA. Here, we established HRM parameters to evaluate the promoter methylation status of the ABCB1 gene. Our study is the first to standardize the HRM dissociation curve to evaluate ABCB1 gene methylation. The association between ABCB1 methylation status and gene expression in established cancer cell lines shows that this method is accurate and reliable.

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“…Kantharidis et al used 5-deoxyazacytidine(5-AZA) to treat tumor cells in which P170 glycoprotein was absent. It changed MDR1 promoter region into hypomethylation status and induced the occurrence of multi-drug resistance in these cells [7,11] . In Blanca's work using an MCF-7/Adr-resistant well-established model, they demonstrated that DNA hypermethylation leads to drug resistance that can be reverted by either down-regulating DNA methyltransferase genes by antisense oligonucleotides or by pharmacologic reversion of methylation by hydralazine, a known DNA methylation inhibitor [3] .…”

Section: Discussionmentioning

confidence: 99%

Relationship between methylation status of multi-drug resistance protein(MRP) and multi-drug resistance in lung cancer cell lines

Liu

Zhong

2007

Chin. J. Cancer Res.

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Objective:To study the relationship between the methylation status of multi-drug resistance protein (MRP) gene and the expression of its mRNA and protein in lung cancer cell lines. Methods: Human embryo lung cell line WI-38, lung adenocarcinoma cell line SPCA-1 and its drug-resistant cells induced by different concentrations of doxorubicin were treated with restriction endonuclease Eco47III. The methylation status of MRP was examined by PCR, and the expressions of its mRNA and protein were evaluated by in situ hybridization and immunohistochemistry. Results: MRP gene promoter region of WI-38 cells was in hypermethylation status, but the promoter region of MRP in SPCA-1 cells and their resistant derivatives induced by different concentrations of doxorubicin were in hypomethylation status. There were significant differences in the expression of MRP mRNA among WI-38 cell line, SPCA-1 cells and their drug-resistant derivatives induced by different concentration of doxorubicin. Consistently, MRP immunostaining presented similar significant differences. Conclusion: The promoter region of MRP in SPCA-1 lung adenocarcinoma cells was in hypomethylation status. The hypomethylation status of 5' regulatory region of MRP promoter is an important structural basis that can increase the activity of transcription and results in the development of drug resistance in lung cancer.

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Decitabine (5-Aza-2′-deoxycytidine) decreased DNA methylation and expression of MDR-1 gene in K562/ADM cells

Cited by 48 publications

References 21 publications

Pharmacogenetics and pharmacoepigenetics of gemcitabine

Pharmacogenetics and pharmacoepigenetics of gemcitabine

Accurate monitoring of promoter gene methylation with high-resolution melting polymerase chain reaction using the ABCB1 gene as a model

Relationship between methylation status of multi-drug resistance protein(MRP) and multi-drug resistance in lung cancer cell lines

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