The CCAAT Enhancer-Binding Protein-α Negatively Regulates the Transactivation of Androgen Receptor in Prostate Cancer Cells

• Published in: Molecular endocrinology (Baltimore, Md.) Md.), 2006-05, Vol.20 (5), p.984-995
• Main Authors: Chattopadhyay, Soma, Gong, Eun-Yeung, Hwang, Miok, Park, Eunsook, Lee, Hyun Joo, Hong, Cheol Yi, Choi, Hueng-Sik, Cheong, Jae-Hun, Kwon, Hyuk Bang, Lee, Keesook
• Format: Article
• Language: English
• Subjects: Androgen Receptor Antagonists; Animals; CCAAT-Enhancer-Binding Protein-alpha - analysis; CCAAT-Enhancer-Binding Protein-alpha - metabolism; Cell Line, Tumor; Cell Proliferation; Down-Regulation; Gene Expression Regulation, Neoplastic; Humans; Male; Promoter Regions, Genetic; Prostate - chemistry; Prostate - growth & development; Prostate - metabolism; Prostate-Specific Antigen - genetics; Prostatic Neoplasms - chemistry; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Rats; Receptors, Androgen - genetics; Receptors, Androgen - metabolism; Repressor Proteins - analysis; Repressor Proteins - metabolism; Transcriptional Activation
• ISSN: 0888-8809; 1944-9917
• DOI: 10.1210/me.2005-0240

The basic leucine zipper transcription factor, CCAAT enhancer-binding protein-α (C/EBPα), negatively regulates cell proliferation and induces terminal differentiation of various cell types. C/EBPα is expressed in the prostate, but its potential role in the tissue is unknown. Herein, we show that C/EBPα is highly expressed at the stage of growth arrest during prostate development. Furthermore, overexpression of C/EBPα decreases the rate of DNA synthesis in LNCaP prostate cancer cells. Investigation of the potential cross-talk between C/EBPα and androgen receptor (AR) that is responsible for androgen-dependent prostate proliferation demonstrates that androgen-dependent transactivation of AR is strongly repressed by C/EBPα. C/EBPα directly binds AR in vitro and forms a complex with AR in vivo. C/EBPα neither prevents the nuclear translocation of AR nor disrupts the N/C-terminal interaction of AR, which are both necessary for its proper transactivation activity upon ligand binding. To modulate AR transactivation, however, C/EBPα does compete with AR coactivators for AR binding. Additionally, C/EBPα is recruited onto AR-target promoters with AR and is further able to inhibit the expression of endogenous prostate-specific antigen in prostate cancer cells. Our results suggest C/EBPα as a potent AR corepressor and provide insight into the role of C/EBPα in prostate development and cancer.