Abstract
The androgen receptor (AR) is expressed in most human prostate cancers. It can be activated in a hypersensitive manner by androgens, nonandrogenic steroids, nonsteroidal anti-androgens and in a ligand-independent manner. IL-6 is a proinflammatory cytokine that activates several signaling pathways. It can either stimulate or inhibit growth of prostate cancer cells. IL-6 is an important positive regulator of AR activity and can stimulate the expression of prostate-specific antigen in a ligand-independent manner. IL-6/AR interaction may either result in growth stimulation (MDA PCa 2b cells) or inhibition (LAPC-4 cells). IL-8 and IL-4 have also been observed to activate AR. Cells generated by prolonged treatment with IL-6 acquire a growth advantage. There are several therapeutic options to target IL-6 in prostate cancer and most laboratory studies have been performed with the monoclonal antibody siltuximab. Endogenous suppressors of cytokine signaling (SOCS)-3 and -1 are expressed in prostate cancer tissue. SOCS-3 inhibits apoptosis in AR-negative cells. However, in androgen-sensitive prostate cancer cell lines, SOCS-3 is induced by androgen and blocks its effects on proliferation and secretion. It is currently understood that there are numerous interactions between androgen and IL-6 signaling in human prostate cancer.
Published Version
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