TNFR2 promotes Adriamycin resistance in breast cancer cells by repairing DNA damage

  • Authors:
    • Fuqian Yang
    • Nana Zhao
    • Nan Wu
  • View Affiliations

  • Published online on: June 30, 2017     https://doi.org/10.3892/mmr.2017.6898
  • Pages: 2962-2968
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Abstract

In recent years, tumor necrosis factor receptor 2 (TNFR2) has attracted increasing attention for its important roles in promoting proliferation, migration and angiogenesis in several types of cancer. However, its role in drug resistance remain unclear. In the present study, TNFR2 expression levels in MDA‑MB‑231 and MCF‑7 breast cancer cells were demonstrated to be associated with Adriamycin (ADM) resistance. Silencing of TNFR2 in MCF‑7 cells significantly inhibited ADM resistance, while overexpression of TNFR2 in MDA‑MB‑231 cells significantly enhanced ADM resistance. ADM treatment induced phosphorylation of the histone family 2A variant X (pH2AX), an established marker of DNA damage. Silencing of TNFR2 in MCF‑7 cells further induced pH2AX levels but inhibited the expression of the DNA damage repair protein, poly(ADP‑ribose) polymerase (PARP). By contract, overexpression of TNFR2 in MDA‑MB‑231 cells decreased pH2AX levels and enhanced PARP expression. Of note, treatment with the PARP inhibitor ABT888 significantly abrogated the effects of TNFR2 on pH2AX expression. On a molecular mechanism level, TNFR2 significantly affected the phosphorylation of AKT serine/threonine kinase 1 (AKT) in both cell lines, and treatment with the AKT inhibitor LY294002 effectively abrogated TNFR2‑induced PARP expression. A drug resistance assay demonstrated that treatment with either LY294002 or ABT888 inhibited ADM resistance in breast cancer cells, and combination treatment with both LY294002 and ABT888 exhibited a significantly stronger inhibition effect on ADM resistance. The present results indicated that TNFR2 promoted ADM resistance in breast cancer cells by regulating the DNA damage repair protein PARP via the AKT signaling pathway.
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September-2017
Volume 16 Issue 3

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

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Spandidos Publications style
Yang F, Zhao N and Wu N: TNFR2 promotes Adriamycin resistance in breast cancer cells by repairing DNA damage. Mol Med Rep 16: 2962-2968, 2017
APA
Yang, F., Zhao, N., & Wu, N. (2017). TNFR2 promotes Adriamycin resistance in breast cancer cells by repairing DNA damage. Molecular Medicine Reports, 16, 2962-2968. https://doi.org/10.3892/mmr.2017.6898
MLA
Yang, F., Zhao, N., Wu, N."TNFR2 promotes Adriamycin resistance in breast cancer cells by repairing DNA damage". Molecular Medicine Reports 16.3 (2017): 2962-2968.
Chicago
Yang, F., Zhao, N., Wu, N."TNFR2 promotes Adriamycin resistance in breast cancer cells by repairing DNA damage". Molecular Medicine Reports 16, no. 3 (2017): 2962-2968. https://doi.org/10.3892/mmr.2017.6898