Epigenetic regulation mechanism of ABCG2 induced drug-resistant phenotype

Abstract

The aim of this study is to investigate epigenetic mechanism of ABCG2 induced drug-resistance. It is not only expatiate for drug-resistance regulation mechanism in all-round, but also to provide scientific experimental basis for selecting target to reverse its drug-resistance. Apply methylation-specific PCR (MSP) to have tested methylation of ABCG2 promoter region −359 to −353 specific positions in breast cancer tissues and paired adjacent tissue of 22 cases, and test their methylation positions with MSP products for sequencing; and adopt fluorescent quantitation RT-PCR to test expression level DNMT1, DNMT3A, DNMT3B and ABCG2; to make analysis on relationship between them with statistical spearman correlation. Specific positions of ABCG2 gene promoter region of 18 cases among the 22 cases with breast cancer (18/22, 82%) existed high methylation ( P<0.05), MSP products sequencing proved methylation of the specific position, and mRNA expression level was relative higher in remarkable positive correlation ( P<0.05). ABCG2, DNMT1, DNMT3A, DNMT3B mRNA expression levels in breast cancer tissues were obviously higher than adjacent tissues ( P<.01), and DNMT3B expression level was obviously higher than DNMT1 and DNMT3A ( P<.01) in negative correlation with ABCG2 gene expression (P=0.001). −359 to −353 positions of promoter regions of ABCG2 gene existed high methylation capable to push expression of this gene in beast cancer tissue. DNMT3B is involved in expression regulation in ABCG2 gene, and provides new scientific basis for drug-resistance target as reverse ABCG2 induction