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.