C/EBP? is a downstream mediator of IL-6 induced growth inhibition of prostate cancer cells
- 1 May 2005
- journal article
- Published by Wiley in The Prostate
- Vol. 63 (2), 143-154
- https://doi.org/10.1002/pros.20159
Abstract
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.This publication has 38 references indexed in Scilit:
- C/EBPϵ interacts with retinoblastoma and E2F1 during granulopoiesisBlood, 2004
- An AU-rich element in the 3′ untranslated region of the C/EBPδ mRNA is important for protein binding during G0 growth arrestBiochemical and Biophysical Research Communications, 2003
- Posttranscriptional and Posttranslational Regulation of C/EBPδ in G0 Growth-arrested Mammary Epithelial CellsPublished by Elsevier BV ,2003
- CCAAT/enhancer-binding proteins: structure, function and regulationBiochemical Journal, 2002
- Cancer Statistics, 2002CA: A Cancer Journal for Clinicians, 2002
- Retinoblastoma protein complexes with C/EBP proteins and activates C/EBP‐mediated transcription*Journal of Cellular Biochemistry, 2001
- Signal Transducer and Activator of Transcription 3 Activates CCAAT Enhancer-binding Protein δ Gene Transcription in G0Growth-arrested Mouse Mammary Epithelial Cells and in Involuting Mouse Mammary GlandJournal of Biological Chemistry, 2000
- CCAAT/Enhancer-binding Protein δ Regulates Mammary Epithelial Cell G0 Growth Arrest and ApoptosisJournal of Biological Chemistry, 1999
- CCAAT/Enhancer-binding Protein-δ (C/EBP-δ) Is Induced in Growth-arrested Mouse Mammary Epithelial CellsPublished by Elsevier BV ,1997
- The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53Cell, 1993