title: Thioredoxin Reductase 1 Expression and Castration-recurrent Growth of Prostate Cancer.
abstract: BACKGROUND
  Many genes are differentially expressed between androgen-dependent and androgen-independent prostate cancer (CaP). Differential expression analysis and subtractive hybridization previously identified nine genes expressed in intact mice bearing CWR22 tumors and castrated mice bearing recurrent CWR22 tumors but not in regressed tumors. The objectives of this study were to develop an immunostaining method to dual-label foci of proliferating tumor cells [the origin of castration-recurrent CaP (CR-CaP)], to determine which of the nine candidate proteins were differentially expressed in proliferating versus nonproliferating cells at the onset of growth after castration, and to test preclinical findings using clinical specimens of androgen-stimulated benign prostate (AS-BP) and CaP (AS-CaP) and CR-CaP.
  
  
  METHODS
  Paraffin-embedded, bromodeoxyuridine-injected CWR22 tumors were hydrated, antigen-retrieved using high heat and high pressure, labeled for each of the nine antigens of interest, visualized using peroxidase, and counterstained with hematoxylin. Mean optical density was calculated for proliferating and nonproliferating areas using automated (nuclear staining) or manual (cytoplasmic staining) image analysis. Prostate tissue microarray sections were immunostained and visually scored.
  
  
  RESULTS
  Immunohistochemistry revealed higher nuclear expression of thioredoxin reductase 1 (TrxR1) in proliferating cells than nonproliferating cells (P < .005). There were no statistical differences between cell types in the expression of other proteins. TrxR1 expression was higher (P < .01) in CR-CaP compared with AS-BP or AS-CaP.
  
  
  CONCLUSIONS
  Increased TrxR1 expression in CR-CaP was consistent with increased TrxR1 and BrdU expression at the onset of growth in the CWR22 model. Thioredoxin reductase 1 should be targeted in an attempt to delay or prevent CaP recurrence after castration.
authors.affiliation: Department of Urologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Swaroop S
authors.initials: SS
authors.lastname: Singh
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Oscar Harris
authors.initials: OH
authors.lastname: Ford
authors.forename: Carol S
authors.initials: CS
authors.lastname: Wrzosek
authors.forename: Diana C
authors.initials: DC
authors.lastname: Mehedint
authors.forename: Mark A
authors.initials: MA
authors.lastname: Titus
authors.forename: James L
authors.initials: JL
authors.lastname: Mohler
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