Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways
Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways
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DOI：
10.1074/jbc.m108255200
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发表时间：
2002-03-01
影响因子：
4.8
通讯作者：
Sadar, MD
中科院分区：
文献类型：
--
作者：
Ueda, T;Bruchovsky, N;Sadar, MD
雄激素受体（AR）是一种配体激活的转录因子，介导雄激素的生物反应。然而，非雄激素途径也被证明可以激活 AR。在 LNCaP 人前列腺癌细胞中研究了白细胞介素 6 (IL-6) 和 AR 信号转导途径之间的串扰机制。 IL-6 诱导多个依赖于 AR 的雄激素反应元件驱动的报告基因，增加丝裂原激活蛋白激酶 (MAPK) 的磷酸化，并激活 AR N 末端结构域 (NTD)。 MAPK 和 JAK 抑制剂降低了 IL-6 诱导的 MAPK 磷酸化和 AR NTD 的激活。免疫沉淀和反式激活研究表明，IL-6 处理 LNCaP 细胞后，AR NTD 的氨基酸 234-558 和 STAT3 之间存在直接相互作用。这些结果表明，IL-6 对人 AR NTD 的激活是通过 LNCaP 前列腺癌细胞中的 MAPK 和 STAT3 信号转导途径介导的。
The androgen receptor (AR) is a ligand-activated transcription factor that mediates the biological responses of androgens. However, non-androgenic pathways have also been shown to activate the AR. The mechanism of cross-talk between the interleukin-6 (IL-6) and AR signal transduction pathways was investigated in LNCaP human prostate cancer cells. IL-6 induced several androgen-response element-driven reporters that are dependent upon the AR, increased the phosphorylation of mitogen-activated protein kinase (MAPK), and activated the AR N-terminal domain (NTD). Inhibitors to MAPK and JAK decreased the IL-6-induced phosphorylation of MAPK and activation of the AR NTD. Immunoprecipitation and transactivation studies showed a direct interaction between amino acids 234-558 of the AR NTD and STAT3 following IL-6 treatment of LNCaP cells. These results demonstrate that activation of the human AR NTD by IL-6 was mediated through MAPK and STAT3 signal transduction pathways in LNCaP prostate cancer cells.