TY - JOUR AB - 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. AD - Department of Breast Surgery, Cancer Hospital, Fudan University, Shanghai 200032, P.R. China null Department of Breast Surgery, Cancer Hospital, Fudan University, 21st District, Dong'an Road 270, Shanghai 200032, P.R. China AU - Shi,Pengcheng AU - Zhang,Yan AU - Tong,Xiaowen AU - Yang,Yu AU - Shao,Zhiming DA - 2011/07/01 DO - 10.3892/ijmm.2011.677 EP - 114 IS - 1 JO - Int J Mol Med KW - dihydrotestosterone p27 S-phase kinase-associated protein 2 direct binding cell cycle ovarian and breast cancer PY - 2011 SN - 1107-3756 1791-244X SP - 109 ST - Dihydrotestosterone induces p27 degradation via direct binding with SKP2 in ovarian and breast cancer T2 - International Journal of Molecular Medicine TI - Dihydrotestosterone induces p27 degradation via direct binding with SKP2 in ovarian and breast cancer UR - https://doi.org/10.3892/ijmm.2011.677 VL - 28 ER -