Interleukin 6 activates androgen receptor-mediated gene expression through a signal transducer and activator of transcription 3-dependent pathway in LNCaP prostate cancer cells.
Interleukin 6 (IL-6) is a cytokine that regulates not only immune and inflammatory responses but also the growth of some tumors, including prostate carcinomas. IL-6 signals through Janus kinase, signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinase and is also able to induce androgen receptor (AR)-mediated gene activation in prostate cancer, which is an important process in prostate cancer androgen-independent progression. We now show that IL-6- induced AR- mediated gene activation requires the activation of STAT3 by IL-6 in LNCaP prostate cancer cells. In particular, STAT3 associates with AR in an androgen-independent but IL-6-dependent manner. Inhibition of STAT3 rather than mitogen-activated protein kinase results in inhibition of AR- mediated gene activation in response to IL-6. These findings not only identify STAT3 as an important signaling molecule required for IL-6-signaling to induce AR- mediated gene activation in prostate carcinoma cells but also reveal the importance of activated STAT3 in human tumor development and progression.[1]References
- Interleukin 6 activates androgen receptor-mediated gene expression through a signal transducer and activator of transcription 3-dependent pathway in LNCaP prostate cancer cells. Chen, T., Wang, L.H., Farrar, W.L. Cancer Res. (2000) [Pubmed]
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