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IL-6 Overexpression in ERG-Positive Prostate Cancer Is Mediated by Prostaglandin Receptor EP2
Section of Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
Section of Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
Section of Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
Section of Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany; Pathology Department, University Hospital of Luebeck, Luebeck, Germany; Leibniz Research Center Borstel, Borstel, Germany.
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2016 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 186, no 4, p. 974-984Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
New York, USA: Elsevier, 2016. Vol. 186, no 4, p. 974-984
National Category
Cancer and Oncology
Research subject
Oncology; Pathology
Identifiers
URN: urn:nbn:se:oru:diva-49637DOI: 10.1016/j.ajpath.2015.12.009ISI: 000373413900021PubMedID: 27012192Scopus ID: 2-s2.0-84962489661OAI: oai:DiVA.org:oru-49637DiVA, id: diva2:919012
Note

Funding Agencies:

Rudolf Becker-Foundation

Wilhelm Sander Foundation 2011.077.2

German Research Foundation DFG PE1179/9-1  PE1179/11-1  DFG NO787/5-1

University Hospital of Bonn BONFOR O-155.0064

Available from: 2016-04-12 Created: 2016-04-05 Last updated: 2018-07-10Bibliographically approved

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Andrén, Ove

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