Dihydrotestosterone induces p27 degradation via direct binding with SKP2 in ovarian and breast cancer

  • Authors:
    • Pengcheng Shi
    • Yan Zhang
    • Xiaowen Tong
    • Yu Yang
    • Zhiming Shao
  • View Affiliations

  • Published online on: April 14, 2011     https://doi.org/10.3892/ijmm.2011.677
  • Pages: 109-114
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Abstract

The effect of androgens on the prevention or promotion of cell cycle progression in ovarian and breast cancer is controversial. This effect determines the basic rules of how to treat postmenopausal patients properly after surgery. In the present study, we investigated the effects of different androgens, namely dihydrotestosterone (DHT), testosterone and dehydroepiandrosterone (DHEA) in MCF-7 breast cancer and OVCAR-3 ovarian cancer cells. We found that DHT could down-regulate p27, but not p21, within 4 h. Further studies proved that DHT induced p27 degradation through the ubiquitin-proteasome proteolytic pathway. Inhibition of the androgen receptor and of phosphorylation did not hamper the degradation. However, proteolysis inhibitors effectively antagonized the DHT-induced p27 degradation. Knockdown of the S-phase kinase-associated protein 2 (SKP2), rather than of the Kip1 ubiquitination promoting complex 1 (KPC1), also prevented p27 down-regulation. DHT led to the direct binding of p27 to SKP2 independent of the phosphorylation status. Collectively, DHT, but not the other examined androgens regulated the degradation of p27 in MCF-7 and OVCAR-3 cells. Furthermore, SKP2 was shown to act as a DHT receptor.

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July 2011
Volume 28 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Shi P, Zhang Y, Tong X, Yang Y and Shao Z: Dihydrotestosterone induces p27 degradation via direct binding with SKP2 in ovarian and breast cancer. Int J Mol Med 28: 109-114, 2011.
APA
Shi, P., Zhang, Y., Tong, X., Yang, Y., & Shao, Z. (2011). Dihydrotestosterone induces p27 degradation via direct binding with SKP2 in ovarian and breast cancer. International Journal of Molecular Medicine, 28, 109-114. https://doi.org/10.3892/ijmm.2011.677
MLA
Shi, P., Zhang, Y., Tong, X., Yang, Y., Shao, Z."Dihydrotestosterone induces p27 degradation via direct binding with SKP2 in ovarian and breast cancer". International Journal of Molecular Medicine 28.1 (2011): 109-114.
Chicago
Shi, P., Zhang, Y., Tong, X., Yang, Y., Shao, Z."Dihydrotestosterone induces p27 degradation via direct binding with SKP2 in ovarian and breast cancer". International Journal of Molecular Medicine 28, no. 1 (2011): 109-114. https://doi.org/10.3892/ijmm.2011.677