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IL-6 overexpression in ERG-Positive prostate cancer is mediated by prostaglandin receptor EP2

Prostate cancer is the most diagnosed cancer in men and multiple risk factors and genetic alterations have been described. The TMPRSS2-ERG fusion event and the overexpression of the transcription factor ERG are present in approximately 50% of all prostate cancer patients, however, the clinical outco...

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Main Authors: Merz, Constanze (Author) , von Mässenhausen, Anne (Author) , Queisser, Angela (Author) , Vogel, Wenzel (Author) , Andrén, Ove (Author) , Kirfel, Jutta (Author) , Duensing, Stefan (Author) , Perner, Sven (Author) , Nowak, Michael (Author)
Format: Article (Journal)
Language:English
Published: April 2016
In: The American journal of pathology
Year: 2016, Volume: 186, Issue: 4, Pages: 974-984
ISSN:1525-2191
DOI:10.1016/j.ajpath.2015.12.009
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ajpath.2015.12.009
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Author Notes:Constanze Merz, Anne von Mässenhausen, Angela Queisser, Wenzel Vogel, Ove Andrén, Jutta Kirfel, Stefan Duensing, Sven Perner, and Michael Nowak
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Summary:Prostate cancer is the most diagnosed cancer in men and multiple risk factors and genetic alterations have been described. The TMPRSS2-ERG fusion event and the overexpression of the transcription factor ERG are present in approximately 50% of all prostate cancer patients, however, the clinical outcome is still controversial. Prostate tumors produce various soluble factors, including the pleiotropic cytokine IL-6, regulating cellular processes such as proliferation and metastatic segregation. Here, we used prostatectomy samples in a tissue microarray format and analyzed the co-expression and the clinicopathologic data of ERG and IL-6 using immunohistochemical double staining and correlated the read-out with clinicopathologic data. Expression of ERG and IL-6 correlated strongly in prostate tissue samples. Forced expression of ERG in prostate tumor cell lines resulted in significantly increased secretion of IL-6, whereas the down-regulation of ERG decreased IL-6 secretion. By dissecting the underlying mechanism in prostate tumor cell lines we show the ERG-mediated up-regulation of the prostanoid receptors EP2 and EP3. The prostanoid receptor EP2 was overexpressed in human prostate cancer tissue. Furthermore, the proliferation rate and IL-6 secretion in DU145 cells was reduced after treatment with EP2-receptor antagonist. Collectively, our study shows that the expression of ERG in prostate cancer is linked to the expression of IL-6 mediated by the prostanoid receptor EP2.
Item Description:Gesehen am 04.05.2020
Physical Description:Online Resource
ISSN:1525-2191
DOI:10.1016/j.ajpath.2015.12.009

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