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Genetic variability in the regulation of the expression cluster of MDR genes in patients with breast cancer

Research output: Contribution to journalArticle

Matvey M. Tsyganov, Maxim B. Freidin, Marina K. Ibragimova, Irina V. Deryusheva, Polina V. Kazantseva, Elena M. Slonimskaya, Nadezhda V. Cherdyntseva, Nikolai V. Litviakov

Original languageEnglish
Pages (from-to)251-260
Number of pages10
JournalCancer Chemotherapy and Pharmacology
Volume80
Issue number2
DOIs
Publication statusPublished - Aug 2017

King's Authors

Abstract

PURPOSE:
We aimed to investigate the association between the polymorphism and expression patterns of multiple drug resistance genes (MDR) in breast cancer (BC).
MATERIALS AND METHODS:
The MDR gene expression levels were measured in tumor tissues of 106 breast cancer patients using quantitative real-time PCR. Affymetrix CytoScan™ HD Array chips were used to assess genotypes. Pairwise correlation analysis for ABCB1, ABCC1, ABCC2 and ABCG2 gene expression levels was carried out to reveal co-expression clusters. Associations between SNPs of MDR genes and their preoperative expression levels were assessed using analysis of covariance adjusting for covariates.
RESULTS:
The SNPs associated with the expression of the ABCB1, ABCC1, ABCC2 and ABCG2 genes before NAC were detected. In addition, 21 SNPs associated with the expression of four ABC-transporter genes and involved in the expression regulation were identified. Validation in an independent sample confirmed the association between the MDR cluster genes and 11 SNPs.
CONCLUSIONS:
Four MDR genes: ABCB1, ABCC1, ABCC2 and ABCG2 were shown to form the functional expression cluster in breast tumor. Further studies are required to discover precise mechanisms of the cluster regulation, thereby providing new approaches and targets to combat the development of the MDR phenotype during chemotherapy.

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