Expression data of LNCaP and MDA PCa 2b cells in absence or presence of IL6

Prostate cancer (PCa) development and progression are associated with chronic inflammation. The cytokine interleukin (IL)-6 can influence progression, differentiation, survival, and angiogenesis of PCa. To identify novel pathways that are triggered by IL-6, we performed a gene expression profiling of two PCa cell lines, LNCaP and MDA PCa 2b, under treatment with 5 ng/ml IL-6. Interferon regulatory factor (IRF)9 was identified as one of the most prevalent IL-6 regulated genes in both cell lines. IRF9 is a mediator of type I interferon signaling and acts together with signal transduction and activator of transcription (STAT)1 and 2 to activate transcription of interferon responsive genes. The IL-6 regulation of IRF9 was confirmed at mRNA and protein levels by quantitative real-time PCR and Western blot, respectively, in both cell lines and could be blocked by the anti-IL-6 antibody Siltuximab. Three PCa cell lines with an autocrine IL-6 loop, PC3, DU145, and LNCaP-IL-6+, showed a high expression of IRF9. A tissue microarray with 36 malignant and adjacent 36 benign areas from prostate cancer specimens showed that IRF9 protein expression is moderately elevated in malignant areas and positively correlates with the tissue expression of IL-6. Downregulation and overexpression of IRF9 provided evidence for an interferon-independent role of IRF9 on cellular proliferation of different PCa cell lines. Furthermore, expression of IRF9 was essential to mediate the antiproliferative effects of IFN-2. We concluded that IL-6 is an inducer of IRF9 expression in prostate cancer and a sensitizer for the antiproliferative effects of IFN2.

24

Erb HH, Langlechner RV, Moser PL, Handle F, Casneuf T, Verstraeten K, Schlick B, Schäfer G, Hall B, Sasser K, Culig Z, Santer FR