Dihydrotestosterone Induces p27 Degradation via Direct Binding with SKP2 in Ovarian and Breast Cancer

    April 2011 in “ International Journal of Molecular Medicine ”
    Zhi‐Ming Shao
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    TLDR Dihydrotestosterone causes p27 protein breakdown in ovarian and breast cancer cells by binding with SKP2.
    In this study, researchers investigated the effects of androgens on cell cycle progression in MCF-7 breast cancer and OVCAR-3 ovarian cancer cells. They found that dihydrotestosterone (DHT) specifically down-regulated p27 within 4 hours through the ubiquitin-proteasome pathway, independent of androgen receptor inhibition or phosphorylation. Proteolysis inhibitors and SKP2 knockdown prevented this degradation, indicating that DHT induced p27 degradation via direct binding with SKP2, which acted as a DHT receptor. Other androgens like testosterone and dehydroepiandrosterone (DHEA) did not have the same effect.
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