Publikationsserver der Universitätsbibliothek Marburg

Titel:Expression des Suppressors zytokiner Signalübertragung 3 (SOCS3) in humanem klarzelligem Nierenzellkarzinom versus gesundem Nierengewebe
Autor:Stumpf, Svenja
Weitere Beteiligte: Urbschat, Anja (PD Dr. med.)
Veröffentlicht:2017
URI:https://archiv.ub.uni-marburg.de/diss/z2017/0568
URN: urn:nbn:de:hebis:04-z2017-05681
DOI: https://doi.org/10.17192/z2017.0568
DDC:610 Medizin
Titel (trans.):Expression of suppressor of cytokine signaling 3 (SOCS3) in human clear cell renal cell carcinoma versus healthy renal tissue
Publikationsdatum:2017-09-20
Lizenz:https://creativecommons.org/licenses/by-nc-sa/4.0

Dokument

Schlagwörter:
STAT3, renal cell cancer, Hypernephrom, kidney cancer, Nierenzellkarzinom, suppressor of cytokine signaling 3, SOCS3

Zusammenfassung:
Der suppressor of cytokine signaling 3 (SOCS3) ist ein negativer Gegenspieler des signal transducer and activator of transcription 3 (STAT3). STAT3 selbst ist ein Transkriptionsfaktor und reguliert Zielgene, die bei der Zellproliferation, Differenzierung und Tumorentstehung beteiligt sind. STAT3 liegt im humanen Nierenzellkarzinom phosphoryliert und damit konstitutiv aktiv vor. Wir untersuchten die Expression von SOCS3 in Gewebeproben aus humanem klarzelligen Nierenzellkarzinom sowie dem benachbarten gesunden Nierengewebe von 35 Patienten. Des Weiteren stimulierten wir Caki-1-Zellen, eine kommerziell erhältliche Zelllinie, die aus einem klarzelligen Nierenzellkarzinom stammt, mit den Zytokinen IL-6 und IFN-γ und untersuchten die SOCS3-Expression. SOCS3 wurde in den humanen Gewebeproben auf Genebene mittels Realtime-TaqMan-PCR sowie auf der Ebene des Proteins mittels Westernblot und Immunohistochemie dargestellt. Wir beobachteten eine signifikant niedrigere SOCS3-Expression im Tumorgewebe gegenüber dem gesunden Nierengewebe. Dahingegen zeigte sich das SOCS3-Protein im Tumorgewebe höher exprimiert als im zugehörigen gesunden Nierengewebe. Die Stimulation der Caki-1-Zellen mit IL-6 zeigte keinen Anstieg der SOCS3-Expression. Nach Stimulation mit IFN-γ konnte hingegen ein signifikanter Anstieg festgestellt werden. Aus den Ergebnissen lässt sich entnehmen, dass SOCS3 im klarzelligen Nierenzellkarzinom reguliert ist und daher in der Tumorentstehung und der Tumorausbreitung involviert sein könnte. SOCS3 könnte ein neues Zielprotein in der onkologischen Therapie des klarzelligen Nierenzellkarzinoms sein, da es in der Lage ist, den aktivierten JAK-STAT-Signalweg zu beeinflussen. Ob weitere lokale Faktoren in der Tumormikroumgebung an der SOCS3-Regulation beteiligt sind und welche genaue Funktion SOCS3 auf pSTAT3 im Nierenzellkarzinom hat, lässt sich nur durch weiterführende Untersuchungen beantworten.

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