TGF-beta 1-Induced EMT of Non-Transformed Prostate Hyperplasia Cells Is Characterized by Early Induction of SNAI2/Slug
BACKGROUND. Epithelial mesenchymal transition (EMT) underlying cancer cell invasion and metastasis has been thoroughly studied in prostate cancer. Although EMT markers have been clinically observed in benign prostate hyperplasia, molecular events underlying the onset and progression of EMT in benign prostate cells have not been described. METHODS. EMT in BPH-1 cells was induced by TGF-beta 1 treatment and the kinetics of expression of EMT markers, regulators, and selected miRNAs was assessed by western blotting and quantitative RT-PCR. RESULTS. EMT in BPH-1 cells was accompanied by rapid up-regulation of SNAI2/Slug and ZEB1 transcription factors, while changes in expression levels of ZEB2 and miR-200 family members were observed after extended time intervals. Invasive phenotype with EMT hallmarks, characterizing tumorigenic clones derived from BPH-1 cells, was associated with increased mRNA levels of SNAI2, ZEB1, and ZEB2, but was not associated with significant changes in basal levels of miR-200 family members. RNA interference revealed that SNAI2/Slug is crucial for TGF-beta 1-induced vimentin up-regulation and migration of BPH-1 cells. CONCLUSIONS. This study suggests that in BPH-1 cells the transcription factor SNAI2/Slug is important for EMT initiation, while the ZEB family of transcription factors in cooperation with the miR-200 family may oppose the reversal of the EMT phenotype. Prostate 71: 1332-1343, 2011. (C) 2011 Wiley-Liss, Inc.