FEN1 knockdown improves trastuzumab sensitivity in human epidermal growth factor 2‑positive breast cancer cells

  • Authors:
    • Xue Zeng
    • Xiaofang Che
    • Yun‑Peng Liu
    • Xiu‑Juan Qu
    • Lu Xu
    • Chen‑Yang Zhao
    • Chun‑Lei Zheng
    • Ke‑Zuo Hou
    • Yuee Teng
  • View Affiliations

  • Published online on: August 2, 2017     https://doi.org/10.3892/etm.2017.4873
  • Pages: 3265-3272
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Abstract

Trastuzumab has been widely applied as a treatment for human epidermal growth factor 2 (HER2)‑ overexpressing breast cancer. However, the therapeutic efficacy of trastuzumab is limited. Flap endonuclease 1 (FEN1) is a multifunctional endonuclease that has a crucial role in DNA recombination and repair. Inhibition of FEN1 is associated with the reversal of anticancer drug resistance. However, it is unclear whether FEN1 is involved in trastuzumab resistance. In the present study, it was demonstrated that trastuzumab increases the expression of FEN1, and FEN1 knockdown significantly enhanced the sensitivity of BT474 cells to trastuzumab (P<0.05). It was also revealed that trastuzumab induced HER receptor activation, increased binding with FEN1 and estrogen receptor α (ERα), and upregulated ERα‑target gene transcription (P<0.05). Upon silencing of FEN1 expression with siRNA, activation of HER receptor and FEN1 binding to ERα were decreased, and trastuzumab‑induced ERα target gene upregulation was partially ameliorated (P<0.05). These results suggest that FEN1 may mediate trastuzumab resistance via inducing HER receptor activation and enhancing ERα‑target gene transcription. The findings of the present study indicate a novel role of FEN1 in trastuzumab resistance, suggesting that targeting FEN1 may enhance the efficiency of trastuzumab as a treatment for HER2‑positive breast cancer.

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October-2017
Volume 14 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zeng X, Che X, Liu YP, Qu XJ, Xu L, Zhao CY, Zheng CL, Hou KZ and Teng Y: FEN1 knockdown improves trastuzumab sensitivity in human epidermal growth factor 2‑positive breast cancer cells. Exp Ther Med 14: 3265-3272, 2017
APA
Zeng, X., Che, X., Liu, Y., Qu, X., Xu, L., Zhao, C. ... Teng, Y. (2017). FEN1 knockdown improves trastuzumab sensitivity in human epidermal growth factor 2‑positive breast cancer cells. Experimental and Therapeutic Medicine, 14, 3265-3272. https://doi.org/10.3892/etm.2017.4873
MLA
Zeng, X., Che, X., Liu, Y., Qu, X., Xu, L., Zhao, C., Zheng, C., Hou, K., Teng, Y."FEN1 knockdown improves trastuzumab sensitivity in human epidermal growth factor 2‑positive breast cancer cells". Experimental and Therapeutic Medicine 14.4 (2017): 3265-3272.
Chicago
Zeng, X., Che, X., Liu, Y., Qu, X., Xu, L., Zhao, C., Zheng, C., Hou, K., Teng, Y."FEN1 knockdown improves trastuzumab sensitivity in human epidermal growth factor 2‑positive breast cancer cells". Experimental and Therapeutic Medicine 14, no. 4 (2017): 3265-3272. https://doi.org/10.3892/etm.2017.4873