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 activates androgen receptor-mediated gene expression through a signal transducer and activator of transcription 3-dependent pathway in LNCaP prostate cancer cells.
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发表时间：
2000-04
期刊：
影响因子：
11.2
通讯作者：
Taosheng Chen;Lihua Wang;William L. Farrar
中科院分区：
文献类型：
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作者：
Taosheng Chen;Lihua Wang;William L. Farrar
白细胞介素6（IL-6）是一种细胞因子，不仅调节免疫和炎症反应，而且还调节一些肿瘤（包括前列腺癌）的生长。IL-6通过Janus激酶、信号转导子和转录激活子3（STAT 3）以及丝裂原活化蛋白激酶进行信号传导，并且还能够诱导前列腺癌中雄激素受体（AR）介导的基因活化，这是前列腺癌雄激素非依赖性进展中的重要过程。我们现在表明，IL-6诱导的AR介导的基因激活需要IL-6在LNCaP前列腺癌细胞中激活STAT 3。特别地，STAT 3以雄激素非依赖性但IL-6依赖性的方式与AR相关。抑制STAT 3而不是丝裂原活化蛋白激酶导致响应于IL-6的AR介导的基因活化的抑制。这些发现不仅确定了STAT 3是IL-6信号传导诱导前列腺癌细胞中AR介导的基因活化所需的重要信号分子，而且还揭示了活化的STAT 3在人类肿瘤发展和进展中的重要性。
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.