The CCAAT enhancer-binding protein-alpha negatively regulates the transactivation of androgen receptor in prostate cancer cells

Mol Endocrinol. 2006 May;20(5):984-95. doi: 10.1210/me.2005-0240. Epub 2006 Feb 2.


The basic leucine zipper transcription factor, CCAAT enhancer-binding protein-alpha (C/EBPalpha), negatively regulates cell proliferation and induces terminal differentiation of various cell types. C/EBPalpha is expressed in the prostate, but its potential role in the tissue is unknown. Herein, we show that C/EBPalpha is highly expressed at the stage of growth arrest during prostate development. Furthermore, overexpression of C/EBPalpha decreases the rate of DNA synthesis in LNCaP prostate cancer cells. Investigation of the potential cross-talk between C/EBPalpha and androgen receptor (AR) that is responsible for androgen-dependent prostate proliferation demonstrates that androgen-dependent transactivation of AR is strongly repressed by C/EBPalpha. C/EBPalpha directly binds AR in vitro and forms a complex with AR in vivo. C/EBPalpha 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/EBPalpha does compete with AR coactivators for AR binding. Additionally, C/EBPalpha 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/EBPalpha as a potent AR corepressor and provide insight into the role of C/EBPalpha in prostate development and cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Androgen Receptor Antagonists
  • CCAAT-Enhancer-Binding Protein-alpha
  • Receptors, Androgen
  • Repressor Proteins
  • Prostate-Specific Antigen