PTEN enhances G2/M arrest in etoposide-treated MCF‑7 cells through activation of the ATM pathway

  • Authors:
    • Ruopeng Zhang
    • Li Zhu
    • Lirong Zhang
    • Anli Xu
    • Zhengwei Li
    • Yijuan Xu
    • Pei He
    • Maoqing Wu
    • Fengxiang Wei
    • Chenhong Wang
  • View Affiliations

  • Published online on: March 11, 2016     https://doi.org/10.3892/or.2016.4674
  • Pages: 2707-2714
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Abstract

As an effective tumor suppressor, phosphatase and tensin homolog (PTEN) has attracted the increased attention of scientists. Recent studies have shown that PTEN plays unique roles in the DNA damage response (DDR) and can interact with the Chk1 pathway. However, little is known about how PTEN contributes to DDR through the ATM-Chk2 pathway. It is well-known that etoposide induces G2/M arrest in a variety of cell lines, including MCF-7 cells. The DNA damage-induced G2/M arrest results from the activation of protein kinase ataxia telangiectasia mutated (ATM), followed by the activation of Chk2 that subsequently inactivates CDC25C, resulting in G2/M arrest. In the present study, we assessed the contribution of PTEN to the etoposide-induced G2/M cell cycle arrest. PTEN was knocked down in MCF-7 cells by specific shRNA, and the effects of PTEN on the ATM-Chk2 pathway were investigated through various approaches. The results showed that knockdown of PTEN strongly antagonized ATM activation in response to etoposide treatment, and thereby reduced the phosphorylation level of ATM substrates, including H2AX, P53 and Chk2. Furthermore, depletion of PTEN reduced the etoposide-induced phosphorylation of CDC25C and strikingly compromised etoposide-induced G2/M arrest in the MCF-7 cells. Altogether, we demonstrated that PTEN plays a unique role in etoposide-induced G2/M arrest by facilitating the activation of the ATM pathway, and PTEN was required for the proper activation of checkpoints in response to DNA damage in MCF-7 cells.
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May-2016
Volume 35 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhang R, Zhu L, Zhang L, Xu A, Li Z, Xu Y, He P, Wu M, Wei F, Wang C, Wang C, et al: PTEN enhances G2/M arrest in etoposide-treated MCF‑7 cells through activation of the ATM pathway. Oncol Rep 35: 2707-2714, 2016
APA
Zhang, R., Zhu, L., Zhang, L., Xu, A., Li, Z., Xu, Y. ... Wang, C. (2016). PTEN enhances G2/M arrest in etoposide-treated MCF‑7 cells through activation of the ATM pathway. Oncology Reports, 35, 2707-2714. https://doi.org/10.3892/or.2016.4674
MLA
Zhang, R., Zhu, L., Zhang, L., Xu, A., Li, Z., Xu, Y., He, P., Wu, M., Wei, F., Wang, C."PTEN enhances G2/M arrest in etoposide-treated MCF‑7 cells through activation of the ATM pathway". Oncology Reports 35.5 (2016): 2707-2714.
Chicago
Zhang, R., Zhu, L., Zhang, L., Xu, A., Li, Z., Xu, Y., He, P., Wu, M., Wei, F., Wang, C."PTEN enhances G2/M arrest in etoposide-treated MCF‑7 cells through activation of the ATM pathway". Oncology Reports 35, no. 5 (2016): 2707-2714. https://doi.org/10.3892/or.2016.4674