Although a number of reports have investigated the effects of IL-6 family cytokines on prostate cell growth, there is limited information available identifying IL-6 inducible downstream effector genes and their function in growth control. Previous studies have demonstrated that IL-6 treatment results in the activation of signal transducer and activator of transcription3 (STAT3) in prostate cancer cells. The goal of this study was to investigate the influence of IL-6 treatment and activation of the Jak/STAT signal transduction pathway on C/EBPδ gene expression and growth inhibition of human prostate cancer cells.
Expression of C/EBPδ and STAT3 activation were assayed using Northern and Western blotting techniques. Proliferation was assessed by [3H] thymidine incorporation, flow cytometry, and colony formation analyses. The analysis of the transcriptional regulation of C/EBPδ was performed using luciferase-reporter constructs.
In this report, we demonstrate that IL-6 treatment induces STAT3 activation (pSTAT3), pSTAT3 binds to the human C/EBPδ gene promoter and induces its expression. We also demonstrate that C/EBPδ over-expression is capable of suppressing prostate cancer cell growth.
These results demonstrate that C/EBPδ gene expression is increased in IL-6 treated LNCaP cells. Increased C/EBPδ gene expression plays an important role in IL-6/STAT3 mediated growth arrest of LNCaP prostate cancer cells. Ongoing studies are investigating the mechanism by which C/EBPδ controls prostate cancer cell growth and the potential role of C/EBPδ in the survival and chemo resistance of prostate cancer metastasis. © 2004 Wiley-Liss, Inc.