EZH2 inhibition sensitizes tamoxifen‑resistant breast cancer cells through cell cycle regulation

  • Authors:
    • Si Chen
    • Fan Yao
    • Qinghuan Xiao
    • Qiannan Liu
    • Yikun Yang
    • Xuejuan Li
    • Guanglie Jiang
    • Takayoshi Kuno
    • Yue Fang
  • View Affiliations

  • Published online on: November 27, 2017     https://doi.org/10.3892/mmr.2017.8160
  • Pages: 2642-2650
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Abstract

Enhancer of zeste homologue 2 (EZH2), a catalytic subunit of polycomb repressive complex 2, is overexpressed in a number of different tumors including breast cancer, and serves important roles in cell cycle regulation, proliferation, apoptosis, tumorigenesis and drug resistance. However, it remains unclear whether EZH2 contributes to tamoxifen resistance in breast cancer. In the present study, the role of EZH2 in tamoxifen resistance in MCF‑7 cells was investigated. EZH2 was overexpressed in MCF‑7 tamoxifen‑resistant (MCF‑7 TamR) cells. EZH2 overexpression decreased the sensitivity of MCF‑7 cells to tamoxifen, and EZH2 knockdown improved the sensitivity of MCF‑7 TamR cells to tamoxifen. Furthermore, EZH2 knockdown induced cell cycle arrest in MCF‑7 TamR cells, accompanied by a decrease in cyclin D1 expression and an increase in p16 expression. EZH2 knockdown reduced p16 gene methylation in MCF‑7 TamR cells. These findings suggested that EZH2 overexpression may contribute to tamoxifen resistance in breast cancer, and EZH2 inhibition may reverse tamoxifen resistance in breast cancer by regulating the cell cycle via the demethylation of the p16 gene. Thus, EZH2 inhibitors may be effective for treating tamoxifen resistance in breast cancer.
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February-2018
Volume 17 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Chen S, Yao F, Xiao Q, Liu Q, Yang Y, Li X, Jiang G, Kuno T and Fang Y: EZH2 inhibition sensitizes tamoxifen‑resistant breast cancer cells through cell cycle regulation. Mol Med Rep 17: 2642-2650, 2018
APA
Chen, S., Yao, F., Xiao, Q., Liu, Q., Yang, Y., Li, X. ... Fang, Y. (2018). EZH2 inhibition sensitizes tamoxifen‑resistant breast cancer cells through cell cycle regulation. Molecular Medicine Reports, 17, 2642-2650. https://doi.org/10.3892/mmr.2017.8160
MLA
Chen, S., Yao, F., Xiao, Q., Liu, Q., Yang, Y., Li, X., Jiang, G., Kuno, T., Fang, Y."EZH2 inhibition sensitizes tamoxifen‑resistant breast cancer cells through cell cycle regulation". Molecular Medicine Reports 17.2 (2018): 2642-2650.
Chicago
Chen, S., Yao, F., Xiao, Q., Liu, Q., Yang, Y., Li, X., Jiang, G., Kuno, T., Fang, Y."EZH2 inhibition sensitizes tamoxifen‑resistant breast cancer cells through cell cycle regulation". Molecular Medicine Reports 17, no. 2 (2018): 2642-2650. https://doi.org/10.3892/mmr.2017.8160