GPX2 overexpression is involved in cell proliferation and prognosis of castration-resistant prostate cancer
- 22 February 2014
- journal article
- research article
- Published by Oxford University Press (OUP) in Carcinogenesis: Integrative Cancer Research
- Vol. 35 (9), 1962-1967
- https://doi.org/10.1093/carcin/bgu048
Abstract
There is a need for exploration of new therapeutic strategies that target distinct molecular mechanisms of castration-resistant prostate cancer (CRPC) because its emergence following androgen deprivation therapy is a major clinical problem. In this report, we investigated the role of glutathione peroxidase 2 (GPX2) in CRPC. GPX2 expression was analyzed in rat and human CRPC cells. Next, we determined the proliferation rate and level of reactive oxygen species (ROS) in GPX2-small interfering RNA (siRNA)-transfected CRPC cells. For in vivo analysis, siRNA-transfected cells were subcutaneously implanted into normal and castrated nude mice. Further, immunohistochemical and prognostic analyses of GPX2 were performed using human specimens. Silencing of GPX2 caused significant growth inhibition and increased intracellular ROS in both rat (PCai1) and human (PC3) CRPC cells. Flow cytometry and western blot analyses revealed that the decrease in proliferation rate of the GPX2-silenced cells was due to cyclin B1-dependent G2/M arrest. Furthermore, knockdown of Gpx2 inhibited tumor growth of PCai1 cells in castrated mice. Immunohistochemical analyses indicated that expression of GPX2 was significantly higher in residual cancer foci after neoadjuvant hormonal therapy than in hormone naive cancer foci. Moreover, patients with high GPX2 expression in biopsy specimen had significantly lower prostate-specific antigen recurrence-free survival and overall survival than those with no GPX2 expression. These findings suggest that GPX2 is a prognostic marker in CRPC and affects proliferation of prostate cancer under androgen depletion partially through protection against ROS signaling.Keywords
This publication has 25 references indexed in Scilit:
- Redox Control Systems in the Nucleus: Mechanisms and FunctionsAntioxidants and Redox Signaling, 2010
- Cancer Statistics, 2007CA: A Cancer Journal for Clinicians, 2007
- Altered metabolism and mitochondrial genome in prostate cancerJournal of Clinical Pathology, 2006
- The organization and inheritance of the mitochondrial genomeNature Reviews Genetics, 2005
- Prostate cancer epidemiologyThe Lancet, 2003
- Reactive Oxygen Species as Intracellular Messengers During Cell Growth and DifferentiationCellular Physiology and Biochemistry, 2001
- Oxidants, oxidative stress and the biology of ageingNature, 2000
- Role of Reactive Oxygen Species in the Regulation of Physiological Functions.Biological & Pharmaceutical Bulletin, 2000
- Prooxidant-Antioxidant Shift Induced by Androgen Treatment of Human Prostate Carcinoma CellsJNCI Journal of the National Cancer Institute, 1997
- Endocrine-Induced Regression of CancersScience, 1967