Inhibitors of cytokine signaling in prostate cancer

Activation of the transcription factor STAT3 in prostate cancer and in surrounding stroma is under control of endogenous inhibitors of cytokine signaling to which SOCS and PiAS belong. SOCS proteins may inhibit apoptosis but also migration in prostate cancer cells. Different effects of SOCS-3 and -1 were published in the scientific literature. Although SOCS-3 and -1 are expressed at a high level in prostate cancer, SOCS-1 but not SOCS-3 blocks cell cycle progression. Our recent studies are focused on PiAS1, which is expressed in the majority of prostate cancer cells and in tissue specimens. High levels of PiAS1 lead to cellular proliferation and inhibition of p21. PiAS1 is also implicated in the regulation of programmed cell death in human prostate cancer. Since PiAS1 is regulated by androgens and androgen receptor, it may have an important role in prostate cancer progression. PiAS1 interaction with the androgen receptor will be discussed. in summary, the proteins which are largely implicated in control of cellular responses initiated by proinflammatory cytokines (SOCS and PiAS) may stimulate or inhibit progression of human prostate cancer, depending on cellular context. Strategies for inhibition of SOCS and PiAS in human prostate cancer may be therefore justified.