title: High NRBP1 expression in prostate cancer is linked with poor clinical outcomes and increased cancer cell growth.
abstract: BACKGROUND
  We recently established the rationale that NRBP1 (nuclear receptor binding protein 1) has a potential growth-promoting role in cell biology. NRBP1 interacts directly with TSC-22, a potential tumor suppressor gene that is differently expressed in prostate cancer. Consequently, we analyzed the role of NRBP1 expression in prostate cancer cell lines and its expression on prostate cancer tissue microarrays (TMA).
  
  
  METHODS
  The effect of NRBP1 expression on tumor cell growth was analyzed by using RNAi. NRBP1 protein expression was evaluated on two TMAs containing prostate samples from more than 1,000 patients. Associations with clinico-pathological features, the proliferation marker Ki67 and survival data were analyzed.
  
  
  RESULTS
  RNAi mediated silencing of NRBP1 expression in prostate cancer cell lines resulted in reduced cell growth (P < 0.05). TMA analysis revealed NRBP1 protein expression in benign prostate hyperplasia in 6% as compared to 60% in both, high-grade intraepithelial neoplasia and prostate cancer samples. Strong NRBP1 protein expression was restricted to prostate cancer and correlated with higher expression of the proliferation marker Ki67 (P < 0.05). Further, patients with strong NRBP1 protein expression showed poor clinical outcomes (P < 0.05). Analysis of matched localized cancer tissues before and after castration revealed that post-therapy-related repression of NRBP1 expression was significantly associated with better overall survival.
  
  
  CONCLUSIONS
  We demonstrate that expression of NRBP1 is up-regulated during the progression of prostate cancer and that high NRBP1 expression is linked with poor prognosis and enhanced tumor cell growth.
authors.affiliation: Institute for Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Ruiz
authors.forename: Martin
authors.initials: M
authors.lastname: Oeggerli
authors.forename: Markus
authors.initials: M
authors.lastname: Germann
authors.forename: Silvia
authors.initials: S
authors.lastname: Gluderer
authors.forename: Hugo
authors.initials: H
authors.lastname: Stocker
authors.forename: Mariacarla
authors.initials: M
authors.lastname: Andreozzi
authors.forename: George N
authors.initials: GN
authors.lastname: Thalmann
authors.forename: Marco G
authors.initials: MG
authors.lastname: Cecchini
authors.forename: Tobias
authors.initials: T
authors.lastname: Zellweger
authors.forename: Susanna
authors.initials: S
authors.lastname: Stürm
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Koivisto
authors.forename: Heikki J
authors.initials: HJ
authors.lastname: Helin
authors.forename: Edward P
authors.initials: EP
authors.lastname: Gelmann
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Glass
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Gasser
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Terracciano
authors.forename: Alexander
authors.initials: A
authors.lastname: Bachmann
authors.forename: Stephen
authors.initials: S
authors.lastname: Wyler
authors.forename: Lukas
authors.initials: L
authors.lastname: Bubendorf
authors.forename: Cyrill A
authors.initials: CA
authors.lastname: Rentsch
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D005387:Finland / Q000453:epidemiology; D015870:Gene Expression; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate; D013557:Switzerland / Q000453:epidemiology; D046888:Tissue Array Analysis; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C410809:NRBP1 protein, human; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D033921:Vesicular Transport Proteins