The ErbB3-binding protein Ebp1 suppresses androgen receptor-mediated gene transcription and tumorigenesis of prostate cancer cells

Proc Natl Acad Sci U S A. 2005 Jul 12;102(28):9890-5. doi: 10.1073/pnas.0503829102. Epub 2005 Jun 30.


Down-regulation of the androgen receptor (AR) is being evaluated as an effective therapy for the advanced stages of prostate cancer. We report that Ebp1, a protein identified by its interactions with the ErbB3 receptor, down-regulates expression of AR and AR-regulated genes in the LNCaP prostate cancer cell line. Using microarray analysis, we identified six endogenous AR target genes, including the AR itself, that are down-regulated by ebp1 overexpression. Chromatin immunoprecipitation assays revealed that Ebp1 was recruited to the prostate-specific antigen gene promoter in response to the androgen antagonist bicalutamide, suggesting that Ebp1 directly affected the expression of AR-regulated genes in response to androgen antagonists. Ebp1 expression was reduced in cells that had become androgen-independent. Androgens failed to stimulate either the growth of ebp1 transfectants or transcription of AR-regulated reporter genes in these cells. The agonist activity of the antiandrogen cyproterone acetate was abolished in ebp1 transfectants. In severe combined immunodeficient mice, Ebp1 overexpression resulted in a reduced incidence of LNCaP tumors and slower tumor growth. These findings suggest that Ebp1 is a previously unrecognized therapeutic target for treatment of hormone refractory prostate cancer.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Androgen Antagonists / metabolism
  • Anilides / metabolism
  • Animals
  • Blotting, Western
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • Cyproterone Acetate / metabolism
  • DNA Primers
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Luciferases
  • Male
  • Mice
  • Mice, SCID
  • Nitriles
  • Oligonucleotide Array Sequence Analysis
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / therapy
  • RNA-Binding Proteins
  • Receptor, ErbB-3 / metabolism
  • Receptors, Androgen / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tosyl Compounds


  • Adaptor Proteins, Signal Transducing
  • Androgen Antagonists
  • Anilides
  • Carrier Proteins
  • DNA Primers
  • Nitriles
  • PA2G4 protein, human
  • RNA-Binding Proteins
  • Receptors, Androgen
  • Tosyl Compounds
  • Cyproterone Acetate
  • bicalutamide
  • Luciferases
  • Receptor, ErbB-3