Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 526, Issue 3, Pages 586-591Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2020.03.114
Keywords
Taxane resistance; ABCB1; Gene amplification; Epigenetics; Esophageal squamous cell carcinoma
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Funding
- JSPS KAKENHI [17K09641, 15K10084, 26460468, 26462074]
- Grants-in-Aid for Scientific Research [17K09641, 26462074, 15K10084] Funding Source: KAKEN
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Taxanes are applied as potent chemotherapeutic agents in the treatment of patients with esophageal cancer, but their usefulness is limited, partly because of acquisition of chemoresistance. In our previous study, we established three taxane resistant esophageal cancer cell lines; significant ABCB1 upregulations were found in all three. However, the responsible mechanism(s) still remains an open question. In this study, we explored possible mechanisms that might contribute to upregulation of ABCB1 in taxane resistant cells. ABCB1 gene amplification was found in taxane resistant cell line RTE-1P, but expressional upregulation cannot be explained only by gene amplification, because gene amplification is one order of magnitude or less whereas gene expression is more than two orders of magnitude. In the parental TE-1, ABCB1 expression was upregulated after treatment with 5-azadeoxycytidine and/or trichostatin A; epigenetic mechanisms may be deeply involved. ABCB1 has two promoters; a downstream promoter was found to play the dominant role in taxane resistant esophageal cancer cell lines. Analyses of CpG islands demonstrated that taxane resistant cells showed unmethylated CGI whereas parental cells were dominantly methylated. In conclusion, we propose that both the ABCB1 gene amplification and aberrations in epigenetic mechanisms are responsible for acquisition of taxane resistance in esophageal cancer cells. (C) 2020 Elsevier Inc. All rights reserved.
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