Methylation patterns of genes coding for drug-metabolizing enzymes in tamoxifen-resistant breast cancer tissues.

Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
Sun Jung KimJungsil Ro

Abstract

The biological mechanisms underlying resistance to tamoxifen are of considerable clinical significance. However, little is known about the correlation between tamoxifen resistance and methylation of genes related to drug-metabolizing enzymes. To address this issue, we examined the methylation pattern and expression of the selected genes coding for drug-metabolizing enzymes, including COMT, CYP1A1, CYP2D6, NAT1, and SULT1A1 in tamoxifen-resistant and control breast cancers. Bisulfite genomic sequencing and methylation-specific PCR were carried out to evaluate the methylation patterns of the five genes from control (n = 74) and tamoxifen-resistant tissues (n = 37) chosen by an age-matched sampling method. Also, end-point reverse transcriptase polymerase chain reaction (RT-PCR) and real-time RT-PCR were performed to determine RNA expression of the genes. Bisulfite genomic sequencing revealed methylation of the NAT1 gene in 25 of the control cancers (33.8%) and 23 of the resistant tumors (62.2%). Of the five genes, only NAT1 showed a significant lower methylation rate in the control group than in the resistant group (p = 0.004). No significant difference of the methylation rate was found in the other four genes including COMT, CYP1...Continue Reading

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Citations

Nov 9, 2010·FEBS Letters·Yi-Wen HuangLi-Shu Wang
Dec 29, 2015·Cancer Chemotherapy and Pharmacology·Jin-Feng LvLan Fan
Sep 18, 2014·Journal of Clinical Pharmacy and Therapeutics·J TangX-P Chen
Apr 12, 2016·Clinical Pharmacology and Therapeutics·P FiselM Schwab
Nov 20, 2016·Expert Opinion on Drug Metabolism & Toxicology·Aleksandra Majchrzak-Celińska, Wanda Baer-Dubowska
Nov 18, 2011·Pharmacological Reviews·Neville J Butcher, Rodney F Minchin
Jul 1, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jiaqi WangSu Zeng

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