Royal College of Surgeons in Ireland
Peroxiredoxin-1 protects estrogen receptor α from oxidative ....pdf (1.88 MB)

Peroxiredoxin-1 protects estrogen receptor α from oxidative stress-induced suppression and is a protein biomarker of favorable prognosis in breast cancer

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posted on 2022-12-01, 16:28 authored by Patrick C O'Leary, Marta Terrile, Malgorzata Bajor, Pawel Gaj, Bryan HennessyBryan Hennessy, Gordon B Mills, Agnieszka Zagozdzon, Darran O'ConnorDarran O'Connor, Donal J. Brennan, Kate Connor, Jane Li, Ana Maria Gonzalez-Angulo, Han-Dong Sun, Jian-Xin Pu, Fredrik Pontén, Mathias Uhlén, Karin Jirström, Dominika A Nowis, John P Crown, Radoslaw Zagozdzon, William M Gallagher

Introduction: Peroxiredoxin-1 (PRDX1) is a multifunctional protein, acting as a hydrogen peroxide (H2O2) scavenger, molecular chaperone and immune modulator. Although differential PRDX1 expression has been described in many tumors, the potential role of PRDX1 in breast cancer remains highly ambiguous. Using a comprehensive antibody-based proteomics approach, we interrogated PRDX1 protein as a putative biomarker in estrogen receptor (ER)-positive breast cancer.

Methods: An anti-PRDX1 antibody was validated in breast cancer cell lines using immunoblotting, immunohistochemistry and reverse phase protein array (RPPA) technology. PRDX1 protein expression was evaluated in two independent breast cancer cohorts, represented on a screening RPPA (n = 712) and a validation tissue microarray (n = 498). In vitro assays were performed exploring the functional contribution of PRDX1, with oxidative stress conditions mimicked via treatment with H2O2, peroxynitrite, or adenanthin, a PRDX1/2 inhibitor.

Results: In ER-positive cases, high PRDX1 protein expression is a biomarker of improved prognosis across both cohorts. In the validation cohort, high PRDX1 expression was an independent predictor of improved relapse-free survival (hazard ratio (HR) = 0.62, 95% confidence interval (CI) = 0.40 to 0.96, P = 0.032), breast cancer-specific survival (HR = 0.44, 95% CI = 0.24 to 0.79, P = 0.006) and overall survival (HR = 0.61, 95% CI = 0.44 to 0.85, P = 0.004). RPPA screening of cancer signaling proteins showed that ERα protein was upregulated in PRDX1 high tumors. Exogenous H2O2 treatment decreased ERα protein levels in ER-positive cells. PRDX1 knockdown further sensitized cells to H2O2- and peroxynitrite-mediated effects, whilst PRDX1 overexpression protected against this response. Inhibition of PRDX1/2 antioxidant activity with adenanthin dramatically reduced ERα levels in breast cancer cells.

Conclusions: PRDX1 is shown to be an independent predictor of improved outcomes in ER-positive breast cancer. Through its antioxidant function, PRDX1 may prevent oxidative stress-mediated ERα loss, thereby potentially contributing to maintenance of an ER-positive phenotype in mammary tumors. These results for the first time imply a close connection between biological activity of PRDX1 and regulation of estrogen-mediated signaling in breast cancer


Irish Research Council for Science, Engineering, and Technology (IRCSET)

Science Foundation Ireland through the Molecular Therapeutics for Cancer Ireland Strategic Research Cluster (award 08/SRC/B1410)

7th European Community Framework Programme (Marie Curie International Reintegration Grant No. 224865; FP7-REGPOT-2012-CT2012-316254-BASTION)

Polish National Science Center (No. 2012/07/B/NZ7/ 04183)

Ministry of Science and Higher Education (IP2012 048172)

Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT Grant (CCRC13GAL)

UICC provided two International Cancer Technology Transfer Fellowships (ICRETT Application No. ICR/11/002/2011; ICR/12/017/2012)

Programme for Third Level Institutions (PRTLI), as administered by the Higher Education Authority (HEA) of Ireland.



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Published Citation

O'Leary PC. et al. Peroxiredoxin-1 protects estrogen receptor α from oxidative stress-induced suppression and is a protein biomarker of favorable prognosis in breast cancer. Breast Cancer Res. 2014;16(4):R79.

Publication Date

10 July 2014

PubMed ID



  • Beaumont Hospital
  • Medicine


BioMed Central


  • Published Version (Version of Record)