Relation of promoter methylation of mdr-1 gene and histone acetylation status with multidrug resistance in MCF-7/Adr cells.
- Author:
Chenghui HUANG
1
;
Peiguo CAO
;
Zhaoxia XIE
Author Information
1. Department of Oncology, Third Xiangya Hospital, Central South University, Changsha 410013, China. hchdoctor@sohu.com
- Publication Type:Journal Article
- MeSH:
ATP Binding Cassette Transporter, Subfamily B, Member 1;
genetics;
Acetylation;
Breast Neoplasms;
pathology;
Cell Line, Tumor;
DNA (Cytosine-5-)-Methyltransferase 1;
DNA (Cytosine-5-)-Methyltransferases;
genetics;
metabolism;
DNA Methylation;
genetics;
Drug Resistance, Multiple;
genetics;
Drug Resistance, Neoplasm;
genetics;
Epigenesis, Genetic;
Female;
Histone Deacetylases;
genetics;
metabolism;
Histones;
chemistry;
Humans;
Promoter Regions, Genetic;
genetics;
RNA, Messenger;
genetics;
metabolism
- From:
Journal of Central South University(Medical Sciences)
2009;34(5):369-374
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To analyze the mdr-1 gene promoter methylation and histone acetylation status in both MCF-7/Adr and MCF-7 cells and to preliminarily explore the epigenetic mechanism of multidrug resistance in breast cancer.
METHODS:mdr-1 gene promoter methylation status of the 2 cell lines was detected by methylation-sensitive PCR. mRNA expression of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) was detected by real-time quantitative PCR. Acetylation level of histone H3 and H4 was examined by optical density assay.
RESULTS:Promoter hypermethylation of mdr-1 gene was observed in MCF-7 cells whereas hypomethylation was found in MCF-7/Adr cells. Expression of DNMT1, DNMT3a, and DNMT3b mRNA in MCF-7/Adr cells significantly decreased compared with that of MCF-7 cells (P<0.05). H3 and H4 histone acetylation levels of MCF-7/Adr cells were obviously higher than those of the MCF-7 cells (P<0.01). Expression of HDAC1, HDAC2, HDAC7, and Sirtuin type 1 (SIRT1) mRNA in MCF-7/Adr cells was significantly reduced (P<0.05).
CONCLUSION:Hypomethylation of the promoter region of mdr-1 gene, high H3 and H4 histone acetylation, and low mRNA expression of DNMTs and HDACs may be important epigenetic factors for the development of MDR in MCF-7/ Adr cells.
