title: EBP1 inhibits translation of androgen receptor mRNA in castration resistant prostate cancer cells.
abstract: BACKGROUND
  Therapies that inhibit androgen receptor (AR) are needed for treatment of castration-resistant prostate cancer (CRPC). The ErbB3 binding protein 1 (EBP1) reduces protein expression of both AR and its target genes in CRPC. Although EBP1 regulates AR in hormone-sensitive prostate cancer cells, by both destabilizing AR mRNA and inhibiting protein translation, the mechanism of EBP1 down regulation of AR in CRPC is unknown.
  
  
  METHODS
  Western blot and quantitative PCR analysis of cell lysates and polysomes were used to assess AR mRNA, protein expression and translation.
  
  
  RESULTS
  In contrast to hormone- dependent cells, EBP1 did not change steady state levels of AR mRNA or AR mRNA stability in hormone refractory cells. EBP1 did slow protein translation of AR mRNA. The ErbB3/4 ligand heregulin further diminished AR translation in EBP1 -transfected cells, but not in control cells.
  
  
  CONCLUSIONS
  These studies suggest that one pathway of EBP1 down-regulation of AR levels may be lost in CRPC.
authors.affiliation: Greenebaum Cancer Center, University of Maryland School of Medicine, 655 West Baltimore Street, BRB 9-029, Baltimore, MD 21201, U.S.A.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Yuexing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Anne W
authors.initials: AW
authors.lastname: Hamburger
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020890:Neuregulin-1 / Q000494:pharmacology; D009919:Orchiectomy; D010766:Phosphorylation / Q000187:drug effects; D011132:Polyribosomes / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011944:Receptors, Androgen / Q000096:biosynthesis* / Q000235:genetics*; D014162:Transfection
chemical_list: C410798:AR protein, human; D048868:Adaptor Proteins, Signal Transducing; D015852:Eukaryotic Initiation Factor-2; D020890:Neuregulin-1; C101633:PA2G4 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011944:Receptors, Androgen; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases