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
DOI: https://doi.org/10.17192/z2017.0568
URN: urn:nbn:de:hebis:04-z2017-05681
DDC: 610 Medizin, Gesundheit
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, SOCS3, kidney cancer, suppressor of cytokine signaling 3, Nierenzellkarzinom, renal cell cancer, Hypernephrom

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.

Summary:
The suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of the signal transducer and activator of transcription 3 (STAT3). STAT3 is a transcription factor and controls target genes, which are involved in cell proliferation, differentiation and tumorigenic process. STAT3 is existent in a phosphorylated form in human renal cell carcinoma and is thereby constitutively activated. We investigated the expression of SOCS3 in tissue samples of human clear cell renal cell carcinoma compared with adjacent healthy renal tissue of 35 patients. Furthermore, we stimulated Caki-1-cells, a commercially available cell line which origines from a clear cell renal cell carcinoma, with the cytokines IL-6 and IFN-γ and measured the SOCS3-expression hereafter. The SOCS3-gene was represented by realtime-taqman-PCR in the human tissue samples, the SOCS3-protein was detected by westernblot and immunohistochemistry. We observed a significant lower SOCS3-mRNA-expression in tumor tissue than in adjacent healthy renal tissue. Whereas the SOCS3-protein was higher expressed in tumor tissue than in adjacent healthy renal tissue. The stimulation of Caki-1-cells with IL-6 generated no increase of SOCS3-expression. However, after stimulation with IFN-γ, a significant increase of SOCS3-expression was determined. In conclusion, the results show that SOCS3 is regulated in human clear cell renal cell carcinoma and that it might be involved in tumorigenic process and tumor dissemination. SOCS3 could represent a new target protein in the oncologic therapy of clear cell renal cell carcinoma considering its ability to influence the activated JAK-STAT-pathway. However, further examinations are necessary to investigate whether additional local factors within the tumor microenvironment may be involved in the SOCS3-regulation and to reveal the detailed effect SOCS3 exerts on pSTAT3 in renal cell carcinoma.

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