title: DC-SCRIPT: AR and VDR regulator lost upon transformation of prostate epithelial cells.
abstract: BACKGROUND
  Nuclear receptors (NR), including the Androgen Receptor (AR) and the Vitamin D Receptor (VDR), play an important role in prostate cancer etiology. We recently found that DC-SCRIPT is a prognostic marker in breast cancer and a unique NR coregulator differentially regulating different classes of NRs. Here we investigated the importance of DC-SCRIPT in prostate cancer.
  
  
  METHODS
  DC-SCRIPT mRNA expression was measured by qPCR. Immunohistochemistry was used to detect DC-SCRIPT protein expression. The functional effects of DC-SCRIPT on the transcriptional activity of AR and VDR were assessed by luciferase reporter assays and qPCR assays on well-known AR and VDR target genes.
  
  
  RESULTS
  DC-SCRIPT mRNA was higher in normal than in corresponding malignant prostate tissue but could not be related to disease stage. DC-SCRIPT protein was found in morphologically normal prostate glands and in infiltrating immune cells. Strikingly, DC-SCRIPT protein expression was absent in malignant prostate epithelial tissue and prostate carcinoma cell lines. DC-SCRIPT protein expression appears to be lost prior to the basal cell marker HMW cytokeratin used in prostate carcinoma diagnostics. In addition, our data demonstrated that DC-SCRIPT repressed transcription mediated by wild-type and mutated AR while enhancing VDR mediated transcription. In addition, transient expression of DC-SCRIPT expression in prostate carcinoma cells strongly repressed cell growth.
  
  
  CONCLUSIONS
  DC-SCRIPT is a key regulator of nuclear receptors AR and VDR that play an opposite role in prostate cancer etiology and loss of DC-SCRIPT may be involved in the onset of prostate cancer.
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Marleen
authors.initials: M
authors.lastname: Ansems
authors.forename: Nina
authors.initials: N
authors.lastname: Karthaus
authors.forename: Saartje
authors.initials: S
authors.lastname: Hontelez
authors.forename: Tilly
authors.initials: T
authors.lastname: Aalders
authors.forename: Maaike W
authors.initials: MW
authors.lastname: Looman
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Verhaegh
authors.forename: Jack A
authors.initials: JA
authors.lastname: Schalken
authors.forename: Gosse J
authors.initials: GJ
authors.lastname: Adema
mesh_terms: D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D011944:Receptors, Androgen; D018167:Receptors, Calcitriol; C515832:ZNF366 protein, human