2011
Slabáková, Eva; Pernicová, Zuzana; Slavíčková, Eva; Staršíchová, Andrea; Kozubík, Alois; Souček, Karel
TGF-β1-induced EMT of non-transformed prostate hyperplasia cells is characterized by early induction of SNAI2/Slug. Journal Article
In: The Prostate, vol. 71, no. 12, pp. 1332–1343, 2011, ISSN: 1097-0045 0270-4137, (Place: United States).
Abstract | Links | BibTeX | Tags: *Epithelial-Mesenchymal Transition/genetics, Biomarkers/metabolism, Cell Line, Cell Movement, Homeodomain Proteins/genetics, Humans, Kinetics, Male, Messenger/metabolism, MicroRNAs/metabolism, Neoplasm Invasiveness/genetics, Phenotype, Prostatic Hyperplasia/*physiopathology, Repressor Proteins/genetics, RNA, Snail Family Transcription Factors, Transcription Factors/*biosynthesis/genetics, Transforming Growth Factor beta1/*pharmacology, Up-Regulation/drug effects, Vimentin/metabolism, Zinc Finger E-box Binding Homeobox 2, Zinc Finger E-box-Binding Homeobox 1
@article{slabakova_tgf-1-induced_2011,
title = {TGF-β1-induced EMT of non-transformed prostate hyperplasia cells is characterized by early induction of SNAI2/Slug.},
author = {Eva Slabáková and Zuzana Pernicová and Eva Slavíčková and Andrea Staršíchová and Alois Kozubík and Karel Souček},
doi = {10.1002/pros.21350},
issn = {1097-0045 0270-4137},
year = {2011},
date = {2011-09-01},
journal = {The Prostate},
volume = {71},
number = {12},
pages = {1332–1343},
abstract = {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-β1 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-β1-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.},
note = {Place: United States},
keywords = {*Epithelial-Mesenchymal Transition/genetics, Biomarkers/metabolism, Cell Line, Cell Movement, Homeodomain Proteins/genetics, Humans, Kinetics, Male, Messenger/metabolism, MicroRNAs/metabolism, Neoplasm Invasiveness/genetics, Phenotype, Prostatic Hyperplasia/*physiopathology, Repressor Proteins/genetics, RNA, Snail Family Transcription Factors, Transcription Factors/*biosynthesis/genetics, Transforming Growth Factor beta1/*pharmacology, Up-Regulation/drug effects, Vimentin/metabolism, Zinc Finger E-box Binding Homeobox 2, Zinc Finger E-box-Binding Homeobox 1},
pubstate = {published},
tppubtype = {article}
}
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-β1 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-β1-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.
2010
Starsíchová, Andrea; Lincová, Eva; Pernicová, Zuzana; Kozubík, Alois; Soucek, Karel
TGF-beta1 suppresses IL-6-induced STAT3 activation through regulation of Jak2 expression in prostate epithelial cells. Journal Article
In: Cellular signalling, vol. 22, no. 11, pp. 1734–1744, 2010, ISSN: 1873-3913 0898-6568, (Place: England).
Abstract | Links | BibTeX | Tags: Cell Line, Cell Proliferation, Epithelial Cells/*metabolism, Humans, Interleukin-6/*antagonists & inhibitors/pharmacology, Janus Kinase 2/genetics/*metabolism, Male, Mucin-1/metabolism, Phosphorylation, Prostate/cytology/enzymology/*metabolism, Prostatic Hyperplasia/enzymology/*metabolism, RNA, RNA Interference, Signal Transduction, Smad Proteins/metabolism, Small Interfering/metabolism, STAT3 Transcription Factor/*metabolism, Transforming Growth Factor beta1/*pharmacology
@article{starsichova_tgf-beta1_2010,
title = {TGF-beta1 suppresses IL-6-induced STAT3 activation through regulation of Jak2 expression in prostate epithelial cells.},
author = {Andrea Starsíchová and Eva Lincová and Zuzana Pernicová and Alois Kozubík and Karel Soucek},
doi = {10.1016/j.cellsig.2010.06.014},
issn = {1873-3913 0898-6568},
year = {2010},
date = {2010-11-01},
journal = {Cellular signalling},
volume = {22},
number = {11},
pages = {1734–1744},
abstract = {Chronic inflammation plays an important role in the initiation and progression of various human diseases including benign prostatic hyperplasia or prostate cancer. Here we show that the proinflammatory cytokine interleukin-6 (IL-6) has prosurvival effects and chronically activates the Jak2/STAT3 signalling pathway in a model of benign prostatic hyperplasia (BPH-1). We demonstrate that the antiinflammatory cytokine transforming growth factor-beta1 (TGF-beta1), which also permanently activates its canonical signalling pathway through SMAD proteins in BPH-1 cells, modifies the effects of IL-6 on cell proliferation. Importantly, TGF-beta1 inhibits IL-6 signal transduction by decreasing the phosphorylation levels of STAT3. This effect is associated with decreased expression of Jak2 at both mRNA and protein levels. Moreover, we showed that TGF-beta1 inhibits IL-6-induced expression of the cancer-associated gene MUC1. These observations demonstrated a novel interaction between TGF-beta1 and IL-6 signalling and suggested another mechanism of how defects in TGF-beta signalling, frequently associated with prostate pathologies, can contribute to the disruption of tissue homeostasis.},
note = {Place: England},
keywords = {Cell Line, Cell Proliferation, Epithelial Cells/*metabolism, Humans, Interleukin-6/*antagonists & inhibitors/pharmacology, Janus Kinase 2/genetics/*metabolism, Male, Mucin-1/metabolism, Phosphorylation, Prostate/cytology/enzymology/*metabolism, Prostatic Hyperplasia/enzymology/*metabolism, RNA, RNA Interference, Signal Transduction, Smad Proteins/metabolism, Small Interfering/metabolism, STAT3 Transcription Factor/*metabolism, Transforming Growth Factor beta1/*pharmacology},
pubstate = {published},
tppubtype = {article}
}
Chronic inflammation plays an important role in the initiation and progression of various human diseases including benign prostatic hyperplasia or prostate cancer. Here we show that the proinflammatory cytokine interleukin-6 (IL-6) has prosurvival effects and chronically activates the Jak2/STAT3 signalling pathway in a model of benign prostatic hyperplasia (BPH-1). We demonstrate that the antiinflammatory cytokine transforming growth factor-beta1 (TGF-beta1), which also permanently activates its canonical signalling pathway through SMAD proteins in BPH-1 cells, modifies the effects of IL-6 on cell proliferation. Importantly, TGF-beta1 inhibits IL-6 signal transduction by decreasing the phosphorylation levels of STAT3. This effect is associated with decreased expression of Jak2 at both mRNA and protein levels. Moreover, we showed that TGF-beta1 inhibits IL-6-induced expression of the cancer-associated gene MUC1. These observations demonstrated a novel interaction between TGF-beta1 and IL-6 signalling and suggested another mechanism of how defects in TGF-beta signalling, frequently associated with prostate pathologies, can contribute to the disruption of tissue homeostasis.