Expression des Suppressors zytokiner Signalübertragung 3 (SOCS3) in humanem klarzelligem Nierenzellkarzinom versus gesundem Nierengewebe

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.