GPX2 overexpression is involved in cell proliferation and prognosis of castration resistant prostate cancer
Menée in vitro et in vivo, cette étude suggère l'intérêt de mesurer l'expression du gène GPX2 pour estimer le pronostic d'un cancer de la prostate résistant à la castration
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-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. Flowcytometry and Western blotting analyses revealed that the decrease in proliferation rate of the GPX2 silenced cells was due to cyclin B1-dependent G2/M arrest. Furthermore, knock down 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 naïve 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.
Carcinogenesis , résumé, 2014