Role of IL-6 in regulating the androgen receptor

Abstract

Androgen receptor (AR) is expressed in human prostate cancer in which it could be activated by steroid hormones and nonsteroidal compounds. Interleukin-6 (IL-6) levels are increased in tissues and sera from patients with advanced prostate cancer. AR-negative prostate cancer cell lines express high levels of IL-6. This cytokine may activate signaling pathways of Janus kinase/signal transducers and activators of transcription factors or mitogen-activated protein kinase, thus contributing to tumor cell growth. IL-6 activation of the AR was described by several investigators in various cell lines. This regulation of AR activity is of importance for cellular differentiation, as evidenced by increase of prostate-specific antigen expression. It was shown that the N-terminal region of the AR is required for activation by IL-6. The effect of IL-6 also depends on functional coactivators SRC-1 and p300. Interestingly, cells exposed to a chronic treatment with IL-6 acquire a more malignant phenotype and downregulate AR expression. Further studies are necessary to evaluate whether IL-6/AR axis could be targeted by novel therapies in prostate cancer. © 2009 Springer-Verlag New York.