Open Access

ARTICLE

Relationship between IL-6/ERK and NF-κB: a study in normal and pathological human prostate gland

Gonzalo Rodríguez-Berriguete¹, Angela Prieto¹, Benito Fraile¹, Yosra Bouraoui⁴, Fermín R. de Bethencourt³, Pilar Martínez-Onsurbe², Gabriel Olmedilla², Ricardo Paniagua¹, Mar Royuela¹

1 Department of Cell Biology and Genetics. University of Alcalá, Madrid, Spain
2 Department of Pathology, Príncipe de Asturias Hospital, Madrid, Spain
3 Department of Urology, “La Paz” Hospital, Madrid, Spain
4 Unité d’Immunologie Microbiologie à la Faculté des Science de Bizerte, Tunisie

* Corresponding Author: M. Royuela,

European Cytokine Network 2010, 21(4), 241-250. https://doi.org/10.1684/ecn.2010.0211

Accepted 30 July 2010;

Abstract

Background. There is growing evidence that inflammation is a causal factor in cancer, wherepro-inflammatory cytokines such as IL-6, IL-1 or TNF-α could induce cellular proliferation by activation ofNF-κB. This study focuses on the IL-6/ERK transduction pathway, its relationship with NF-κB, and the conse-quences of dysregulation in the development of prostate pathologies such as benign prostate hyperplasia (BPH),prostate intraepithelial neoplasia (PIN) and prostate cancer (PC). Methods. Immunohistochemical and Westernblot analyses for IL-6, gp-130, Raf-1, MEK-1, ERK-1, p-MEK, ERK-2, p-ERK, NF-κB/p-50 and NF-κB/p-65were carried out in 20 samples of normal prostate glands, 35 samples of BPH, 27 samples with a diagnosis ofPIN (low-grade PIN or high-grade PIN), and 95 samples of PC (23 with low, 51 with medium and 21 with highGleason scores). Results. Immunoreaction to IL-6, gp-130, ERK-1, ERK-2, p-ERK and NF-κB/p50 was found inthe cytoplasm of epithelial cells in normal prostate samples; p-MEK was found in the nucleus of epithelial cells;but not expression to Raf-1, MEK-1 and NF-κB/p65. In BPH, all of these proteins were immunoexpressed, whilethere was increased immunoexpression of IL-6, gp-130, p-MEK, ERK-1, ERK-2 and NF-κB/p50 (cytoplasm).In PC, immunoexpression of IL-6 and gp-130 were similar to that found in BPH; while immunoexpression ofRaf-1, MEK-1, p-MEK, ERK-1, ERK-2, p-ERK, NF-κB/p50 (nucleus and cytoplasm), and NF-κB/p65 (nucleusand cytoplasm) was higher than in BPH. Conclusion. Translocation of NF-κB to the nucleus in PC and high-grade PIN could be stimulated by the IL-6/ERK transduction pathway, but might also be stimulated by othertransduction pathways, such as TNF-α/NIK, TNF/p38, IL-1/NIK or IL-1/p38. Activation of NF-κB in PC couldregulate IL-6 expression. These transduction pathways are also related to activation of other transcriptionfactors such as Elk-1, ATF-2 or c-myc (also involved in cell proliferation and survival). PC is a heterogeneousdisease, where multiple transduction pathways might alter the apoptosis/proliferation balance. Significantattention should be give to the combination of novel agents directed towards inactivation of pro-inflammatorycytokines than can disrupt tumour cell growth.

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