Activation of PKR/eIF2α signaling cascade is associated with dihydrotestosterone‐induced cell cycle arrest and apoptosis in human liver cells

• DOI: 10.1002/jcb.24051
• Publication Date: 2012-01-06T13:52:22Z
• Authors: Rongyang Dai; Dongmei Yan; Juan Li; Shaokun Chen; Youping Liu; Run Chen; Chunyan Duan; Mei Wei; Hong Li; Tao He
• Keywords: Dihydrotestosterone

Abstract Androgen receptor (AR) signaling plays an important role in the development and progression of several liver diseases, including hepatocellular carcinoma (HCC) non‐alcoholic fatty disease (NAFLD). Dihydrotestosterone (DHT) is active metabolite major circulating androgen, testosterone. In this study, we investigated effect DHT on human cells. We found that not only induces cell cycle arrest but also initiates apoptosis androgen‐sensitive cells, such as SMMC‐7721 L02. Importantly, DHT/AR activation RNA‐dependent protein kinase (PKR)/eukaryotic initiation factor‐2 alpha (eIF2α) cascades PKR/eIF2α activation‐induced growth DNA damage‐inducible gene 153 (GADD153) heat shock 27 (Hsp27) expression contribute to response DHT. It notable administration results cells apoptosis, at least part, through PKR/eIF2α/GADD153 cascades. These suggest androgen/AR pathway a pivotal regulating, whose deregulation might be involved pathogenesis diseases. J. Cell. Biochem. 113: 1800–1808, 2012. © 2012 Wiley Periodicals, Inc.