Vorinostat enhances protein stability of p27 and p21 through negative regulation of Skp2 and Cks1 in human breast cancer cells

  • Authors:
    • Norihisa Uehara
    • Katsuhiko Yoshizawa
    • Airo Tsubura
  • View Affiliations

  • Published online on: April 6, 2012     https://doi.org/10.3892/or.2012.1758
  • Pages: 105-110
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Abstract

Vorinostat is a histone deacetylase inhibitor that blocks cancer cell proliferation through the regulation of cyclin-dependent kinase inhibitors. We, herein, examined the involvement of S-phase kinase-associated protein 2 (Skp2) and cyclin-dependent kinase subunit 1 (Cks1), the components of the SCFSkp2-Cks1 (Skp1/Cul1/F-box protein) ubiquitin ligase complex, in the regulation of p27 and p21 during vorinostat-induced growth arrest of MDA-MB-231 and MCF-7 human breast cancer cells. Vorinostat significantly reduced BrdU incorporation in MDA-MB-231 and MCF-7 cells, which was associated with increased p27 and p21 protein levels without concomitant induction of p27 mRNA. Vorinostat-induced accumulation of p27 and p21 proteins was inversely correlated with the mRNA and protein levels of Skp2 and Cks1. Cycloheximide chase analysis revealed that vorinostat increased the half-life of p27 and p21 proteins. The accumulation of p27 and p21 proteins was attenuated by forced expression of Skp2 and Cks1, which conferred resistance to the vorinostat-induced S-phase reduction. These results suggest that vorinostat-induced growth arrest may be in part due to the enhanced protein stability of p27 and p21 through the downregulation of Skp2 and Cks1.

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July 2012
Volume 28 Issue 1

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

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Spandidos Publications style
Uehara N, Yoshizawa K and Tsubura A: Vorinostat enhances protein stability of p27 and p21 through negative regulation of Skp2 and Cks1 in human breast cancer cells. Oncol Rep 28: 105-110, 2012
APA
Uehara, N., Yoshizawa, K., & Tsubura, A. (2012). Vorinostat enhances protein stability of p27 and p21 through negative regulation of Skp2 and Cks1 in human breast cancer cells. Oncology Reports, 28, 105-110. https://doi.org/10.3892/or.2012.1758
MLA
Uehara, N., Yoshizawa, K., Tsubura, A."Vorinostat enhances protein stability of p27 and p21 through negative regulation of Skp2 and Cks1 in human breast cancer cells". Oncology Reports 28.1 (2012): 105-110.
Chicago
Uehara, N., Yoshizawa, K., Tsubura, A."Vorinostat enhances protein stability of p27 and p21 through negative regulation of Skp2 and Cks1 in human breast cancer cells". Oncology Reports 28, no. 1 (2012): 105-110. https://doi.org/10.3892/or.2012.1758