Sanford Daniel C, DeWille James W
Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA.
Prostate. 2005 May 1;63(2):143-54. doi: 10.1002/pros.20159.
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/EBPdelta gene expression and growth inhibition of human prostate cancer cells.
Expression of C/EBPdelta and STAT3 activation were assayed using Northern and Western blotting techniques. Proliferation was assessed by [(3)H] thymidine incorporation, flow cytometry, and colony formation analyses. The analysis of the transcriptional regulation of C/EBPdelta 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/EBPdelta gene promoter and induces its expression. We also demonstrate that C/EBPdelta over-expression is capable of suppressing prostate cancer cell growth.
These results demonstrate that C/EBPdelta gene expression is increased in IL-6 treated LNCaP cells. Increased C/EBPdelta 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/EBPdelta controls prostate cancer cell growth and the potential role of C/EBPdelta in the survival and chemo resistance of prostate cancer metastasis. (c) 2004 Wiley-Liss, Inc.
尽管已有多项报道研究了白细胞介素-6（IL-6）家族细胞因子对前列腺细胞生长的影响，但关于鉴定IL-6诱导的下游效应基因及其在生长控制中的功能的信息有限。先前的研究表明，IL-6处理可导致前列腺癌细胞中信号转导子和转录激活子3（STAT3）的激活。本研究的目的是探讨IL-6处理和Jak/STAT信号转导通路的激活对人前列腺癌细胞C/EBPδ基因表达和生长抑制的影响。
使用Northern和Western印迹技术检测C/EBPδ的表达和STAT3的激活。通过[³H]胸苷掺入、流式细胞术和集落形成分析评估细胞增殖。使用荧光素酶报告构建体对C/EBPδ的转录调控进行分析。
在本报告中，我们证明IL-6处理可诱导STAT3激活（pSTAT3），pSTAT3与人C/EBPδ基因启动子结合并诱导其表达。我们还证明C/EBPδ的过表达能够抑制前列腺癌细胞的生长。
这些结果表明，在IL-6处理的LNCaP细胞中C/EBPδ基因表达增加。C/EBPδ基因表达的增加在IL-6/STAT3介导的LNCaP前列腺癌细胞生长停滞中起重要作用。正在进行的研究正在探讨C/EBPδ控制前列腺癌细胞生长的机制以及C/EBPδ在前列腺癌转移的存活和化疗耐药中的潜在作用。（c）2004威利-利斯公司。
