BMI-1 interacts with sMEK1 and inactivates sMEK1-induced apoptotic cell death

  • Authors:
    • Boh-Ram Kim
    • Youngjoo Kwon
    • Seung Bae Rho
  • View Affiliations

  • Published online on: November 21, 2016     https://doi.org/10.3892/or.2016.5262
  • Pages: 579-586
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Abstract

The B lymphoma Mo-MLV insertion region 1 homolog (BMI-1) protein is activated in various types of tumors and associated with cancer development and tumor progression. However, the working role of BMI-1 in cellular signaling is not understood completely. In this study, we revealed one possible biologic mechanism of BMI-1 in cancer progression in vitro using a human ovarian tumor cell system. Suppressor of MEK1 (sMEK1), a pivotal regulator involved in the cellular biological response mechanism, was identified as a BMI-1-binding protein. Ectopic expression of BMI-1 activated cell growth by reducing sMEK1-stimulated apoptotic cell death and suppressing p21, p27 and p53 expression, while enhancing cyclin D1, CDK4 and Bcl-2 expression. The effect of BMI-1 on cell cycle and apoptotic regulatory proteins was also confirmed via silencing of BMI-1 expression. Subsequently, the promoter activities of p21 and p53 were inactivated significantly. However, BMI-1 overexpression noticeably increased Bcl-2 and NF-κB activities. In addition, BMI-1 activated the PI3K/mTOR/4E-BP1 signaling pathways, and sMEK1 significantly inhibited BMI-1-stimulated oncogenesis. These insights provide evidence that BMI-1 activates cell growth and suppresses apoptosis. Collectively, our data indicate that BMI-1 plays a pivotal role in the progression of ovarian cancer, thus representing a novel target for antitumor therapy of ovarian cancer.
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January-2017
Volume 37 Issue 1

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

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Spandidos Publications style
Kim B, Kwon Y and Rho SB: BMI-1 interacts with sMEK1 and inactivates sMEK1-induced apoptotic cell death. Oncol Rep 37: 579-586, 2017.
APA
Kim, B., Kwon, Y., & Rho, S.B. (2017). BMI-1 interacts with sMEK1 and inactivates sMEK1-induced apoptotic cell death. Oncology Reports, 37, 579-586. https://doi.org/10.3892/or.2016.5262
MLA
Kim, B., Kwon, Y., Rho, S. B."BMI-1 interacts with sMEK1 and inactivates sMEK1-induced apoptotic cell death". Oncology Reports 37.1 (2017): 579-586.
Chicago
Kim, B., Kwon, Y., Rho, S. B."BMI-1 interacts with sMEK1 and inactivates sMEK1-induced apoptotic cell death". Oncology Reports 37, no. 1 (2017): 579-586. https://doi.org/10.3892/or.2016.5262