| Autor: |
Indo S; Laboratory of Cellular and Molecular Oncology, Department of Basic and Clinical Oncology, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.; Center for Cancer Prevention and Control (CECAN), Santiago 8380453, Chile., Orellana-Serradell O; Millennium Nucleus of Ion Channel-Associated Diseases (MiNICAD), Santiago 8380453, Chile., Torres MJ; Laboratory of Cellular and Molecular Oncology, Department of Basic and Clinical Oncology, Faculty of Medicine, University of Chile, Santiago 8380453, Chile., Castellón EA; Laboratory of Cellular and Molecular Oncology, Department of Basic and Clinical Oncology, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.; Center for Cancer Prevention and Control (CECAN), Santiago 8380453, Chile., Contreras HR; Laboratory of Cellular and Molecular Oncology, Department of Basic and Clinical Oncology, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.; Center for Cancer Prevention and Control (CECAN), Santiago 8380453, Chile. |
| Abstrakt: |
The RE-1 silencing transcription factor (REST) is a repressor factor related to neuroendocrine prostate cancer (PCa) (NEPC), a poor prognostic stage mainly associated with castration-resistant PCa (CRPC). NEPC is associated with cell transdifferentiation and the epithelial-mesenchymal transition (EMT) in cells undergoing androgen deprivation therapy (ADT) and enzalutamide (ENZ). The effect of REST overexpression in the 22rv1 cell line (xenograft-derived prostate cancer) on EMT, migration, invasion, and the viability for ENZ was evaluated. EMT genes, Twist and Zeb1, and the androgen receptor (AR) were evaluated through an RT-qPCR and Western blot in nuclear and cytosolic fractions of REST-overexpressing 22rv1 cells (22rv1-REST). The migratory and invasive capacities of 22rv1-REST cells were evaluated via Transwell ® assays with and without Matrigel, respectively, and their viability for enzalutamide via MTT assays. The 22rv1-REST cells showed decreased nuclear levels of Twist, Zeb1, and AR, and a decreased migration and invasion and a lower viability for ENZ compared to the control. Results were expressed as the mean + SD of three independent experiments (Mann-Whitney U test, Kruskal-Wallis, Tukey test). REST behaves like a tumor suppressor, decreasing the aggressiveness of 22rv1 cells, probably through the repression of EMT and the neuroendocrine phenotype. Furthermore, REST could represent a response marker to ENZ in PCa patients. |
