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Abstract
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.
Originalsprache | Englisch |
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Zeitschrift | American Journal of Pathology |
Jahrgang | 186 |
Ausgabenummer | 4 |
Seiten (von - bis) | 974-984 |
Seitenumfang | 11 |
ISSN | 0002-9440 |
DOIs | |
Publikationsstatus | Veröffentlicht - 01.04.2016 |
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Die Rolle der Mediator-Komplex-Untereinheiten MED12 und MED15 in der Entwicklung des androgen-abhängigen Prostatakarzinoms zum kastrations-resistenten Prostatakarzinom.
Perner, S. (Projektleiter*in (PI))
01.01.15 → 31.12.19
Projekt: DFG-Projekte › DFG Einzelförderungen (Sachbeihilfen)