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GPX2 overexpression is involved in cell proliferation and prognosis of castration-resistant prostate cancer.
- Source :
-
Carcinogenesis [Carcinogenesis] 2014 Sep; Vol. 35 (9), pp. 1962-7. Date of Electronic Publication: 2014 Feb 22. - Publication Year :
- 2014
-
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.<br /> (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Adenocarcinoma drug therapy
Adenocarcinoma mortality
Adenocarcinoma pathology
Androgen Antagonists pharmacology
Androgen Antagonists therapeutic use
Animals
Antineoplastic Agents, Hormonal pharmacology
Antineoplastic Agents, Hormonal therapeutic use
Cell Line, Tumor
Disease-Free Survival
Drug Resistance, Neoplasm
Gene Expression
Glutathione Peroxidase genetics
Humans
Male
Mice
Mice, Nude
Multivariate Analysis
Neoplasm Transplantation
Neoplasm, Residual
Prognosis
Proportional Hazards Models
Prostatic Neoplasms, Castration-Resistant drug therapy
Prostatic Neoplasms, Castration-Resistant mortality
Prostatic Neoplasms, Castration-Resistant pathology
RNA Interference
RNA, Small Interfering genetics
Rats
Reactive Oxygen Species metabolism
Adenocarcinoma enzymology
Cell Proliferation
Glutathione Peroxidase metabolism
Prostatic Neoplasms, Castration-Resistant enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2180
- Volume :
- 35
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 24562575
- Full Text :
- https://doi.org/10.1093/carcin/bgu048