Induction of p53 expression and apoptosis by a recombinant dual-target MDM2/MDMX inhibitory protein in wild‑type p53 breast cancer cells

  • Authors:
    • Qian-Qian Geng
    • Dan-Feng Dong
    • Nan-Zheng Chen
    • Yin-Ying Wu
    • En-Xiao Li
    • Jie Wang
    • Shao-Meng Wang
  • View Affiliations

  • Published online on: October 14, 2013     https://doi.org/10.3892/ijo.2013.2138
  • Pages: 1935-1942
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Abstract

The tumor suppressor gene p53 is often inactivated in breast cancer cells due to gene mutation or overexpression of its repressors (such as murine double minute 2 and murine double minute X). Inhibitors of murine double minute 2 (MDM2) and murine double minute X (MDMX) could lead to tumor suppression by restoration of p53 activity and such an approach is a promising strategy for future control of breast cancer. This study aimed to investigate the feasibility of the recombinant MDM2 and MDMX inhibitory protein in control of breast cancer in vitro. A cell-permeable dual-target MDM2/MDMX inhibitory protein was expressed in E. coli and incubated with p53 wild‑type breast cancer cells. The data showed that this recombinant MDM2/MDMX inhibitory protein reduced the viability of MCF-7 and ZR-75-30 breast cancer cell lines and promoted cell cycle arrest and apoptosis by activation and stabilization of the p53 protein. Mechanistically, this MDM2/MDMX inhibitory protein increased the expression of p21, Bax and puma proteins, and inhibitory expression of MDM2 and MDMX proteins. This recombinant protein showed a better in vitro effect than that of nutlin-3α, a small molecule MDM2 inhibitor. The data further support the hypothesis that targeting of the p53 gene pathway could effectively control breast cancer.
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December 2013
Volume 43 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Geng, Q., Dong, D., Chen, N., Wu, Y., Li, E., Wang, J., & Wang, S. (2013). Induction of p53 expression and apoptosis by a recombinant dual-target MDM2/MDMX inhibitory protein in wild‑type p53 breast cancer cells. International Journal of Oncology, 43, 1935-1942. https://doi.org/10.3892/ijo.2013.2138
MLA
Geng, Q., Dong, D., Chen, N., Wu, Y., Li, E., Wang, J., Wang, S."Induction of p53 expression and apoptosis by a recombinant dual-target MDM2/MDMX inhibitory protein in wild‑type p53 breast cancer cells". International Journal of Oncology 43.6 (2013): 1935-1942.
Chicago
Geng, Q., Dong, D., Chen, N., Wu, Y., Li, E., Wang, J., Wang, S."Induction of p53 expression and apoptosis by a recombinant dual-target MDM2/MDMX inhibitory protein in wild‑type p53 breast cancer cells". International Journal of Oncology 43, no. 6 (2013): 1935-1942. https://doi.org/10.3892/ijo.2013.2138