title: Peroxiredoxin-3 is overexpressed in prostate cancer and promotes cancer cell survival by protecting cells from oxidative stress.
abstract: OBJECTIVE
  We have previously identified peroxiredoxin-3 (PRDX-3) as a cell-surface protein that is androgen regulated in the LNCaP prostate cancer (PCa) cell line. PRDX-3 is a member of the peroxiredoxin family that are responsible for neutralising reactive oxygen species.
  
  
  METHODS
  PRDX-3 expression was examined in tissue from 32 patients using immunohistochemistry. Subcellular distribution was determined using confocal microscopy. PRDX-3 expression was determined in antiandrogen-resistant cell lines by western blotting and quantitative RT-PCR. The pathways of PRDX-3 overexpression and knockdown on apoptosis and response to oxidative stress were investigated using protein arrays.
  
  
  RESULTS
  PRDX-3 is upregulated in a number of endocrine-regulated tumours; in particular in PCa and prostatic intraepithelial neoplasia. Although the majority of PRDX-3 is localised to the mitochondria, we have confirmed that PRDX-3 at the cell membrane is androgen regulated. In antiandrogen-resistant LNCaP cell lines, PRDX-3 is upregulated at the protein but not RNA level. Resistant cells also possess an upregulation of the tricarboxylic acid (TCA) pathway and resistance to H₂O₂-induced apoptosis through a failure to activate pro-apoptotic pathways. Knockdown of PRDX-3 restored H₂O₂ sensitivity.
  
  
  CONCLUSIONS
  Our results suggest that PRDX-3 has an essential role in regulating oxidation-induced apoptosis in antiandrogen-resistant cells. PRDX-3 may have potential as a therapeutic target in castrate-independent PCa.
authors.affiliation: Uro-Oncology Research Group, Cambridge CB2 0RE, UK. Hayley.Whitaker@cruk.cam.ac.uk
authors.forename: H C
authors.initials: HC
authors.lastname: Whitaker
authors.forename: D
authors.initials: D
authors.lastname: Patel
authors.forename: W J
authors.initials: WJ
authors.lastname: Howat
authors.forename: A Y
authors.initials: AY
authors.lastname: Warren
authors.forename: J D
authors.initials: JD
authors.lastname: Kay
authors.forename: T
authors.initials: T
authors.lastname: Sangan
authors.forename: J C
authors.initials: JC
authors.lastname: Marioni
authors.forename: J
authors.initials: J
authors.lastname: Mitchell
authors.forename: S
authors.initials: S
authors.lastname: Aldridge
authors.forename: H J
authors.initials: HJ
authors.lastname: Luxton
authors.forename: C
authors.initials: C
authors.lastname: Massie
authors.forename: A G
authors.initials: AG
authors.lastname: Lynch
authors.forename: D E
authors.initials: DE
authors.lastname: Neal
mesh_terms: D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D061105:Peroxiredoxin III / Q000378:metabolism* / Q000502:physiology; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C516115:PRDX3 protein, human; D061105:Peroxiredoxin III