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Differential expression of peroxiredoxins in prostate cancer: Consistent upregulation of PRDX3 and PRDX4
Author(s) -
Basu Anamika,
Banerjee Hiya,
Rojas Heather,
Martinez Shannalee R.,
Roy Sourav,
Jia Zhenyu,
Lilly Michael B.,
De León Marino,
Casiano Carlos A.
Publication year - 2010
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21292
Subject(s) - prostate cancer , tissue microarray , immunohistochemistry , downregulation and upregulation , prostate , prostatectomy , medicine , pathology , pca3 , cancer , oncology , cancer research , biology , gene , genetics
BACKGROUND The peroxiredoxins (PRDXs) are emerging as regulators of antioxidant defense, apoptosis, and therapy resistance in cancer. Because their significance in prostate cancer (PCa) is unclear, we investigated their expression and clinical associations in PCa. METHODS Transcript expression of PRDX1–6 in PCa was evaluated in cancer gene microarray datasets, whereas protein expression was evaluated by immunoblotting in prostate cell lines, and by immunohistochemistry (IHC) in prostate tissue microarrays (TMAs) containing tumor (n = 80) and control (n = 17) tissues. PRDX3 was also analyzed in TMAs containing PCa tissues from African‐American and Caucasian patients (n = 150 per group). PRDX expression was correlated with patients' clinicopathologic characteristics. RESULTS Analysis of PRDX expression in cancer microarray datasets revealed consistent upregulation (tumor vs. normal) of PRDX3 and 4. All PRDXs exhibited elevated protein expression in PCa cell lines, compared with non‐tumor cells. IHC revealed significant overexpression of PRDX3 and 4 in PCa, associated with age, increased prostate specific antigen (PSA), tumor stage, or Gleason score. High PRDX3 staining was associated with early age and elevated Gleason score at time of radical prostatectomy in African‐American but not in Caucasian patients with PCa. PSA recurrence free survival in patients with low PRDX3 tumor expression was significantly longer in Caucasians compared to African‐Americans, but no difference was detected for high expression. CONCLUSIONS PRDXs exhibit differential expression in prostate tumors, with PRDX3 and 4 consistently upregulated. Their role in PCa development, and their potential as biological determinants of PCa health disparities and novel therapeutic targets, deserve further investigation. Prostate 71:755–765, 2011. © 2010 Wiley‐Liss, Inc.