Interleukin-6 differentially regulates androgen receptor transactivation via PI3K-Akt, STAT3, and MAPK, three distinct signal pathways in prostate cancer cells.
Interleukin-6 differentially regulates androgen receptor transactivation via PI3K-Akt, STAT3, and MAPK, three distinct signal pathways in prostate cancer cells.
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DOI：
10.1016/s0006-291x(03)00792-7
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发表时间：
2003-06
影响因子：
3.1
通讯作者：
Lin Yang;Liang Wang;Hui-Kuan Lin;Pu-Yeh Kan;Shaozhen Xie;M. Tsai;Peng-Hui Wang;Yen-Ta Chen;Chawnshang Chang
中科院分区：
文献类型：
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作者：
Lin Yang;Liang Wang;Hui-Kuan Lin;Pu-Yeh Kan;Shaozhen Xie;M. Tsai;Peng-Hui Wang;Yen-Ta Chen;Chawnshang Chang
IL-6对前列腺癌细胞的作用已被充分证明，但仍存在争议。有报道认为IL-6可以促进前列腺癌细胞的生长，也有报道认为IL-6可以抑制前列腺癌细胞的生长。在此，我们系统地研究了前列腺癌细胞中的各种IL-6信号通路，发现IL-6可以通过至少三种不同的通路来调节雄激素受体（AR）的功能，雄激素受体是控制前列腺癌生长的关键转录因子。我们的研究结果表明，IL-6可以通过STAT 3或MAPK途径增强AR反式激活。相比之下，IL-6可以通过PI 3 K-Akt途径抑制AR反式激活。这些不同信号通路的共存可能导致对AR反式激活的相加或冲突效应。总之，我们的研究结果表明，这些不同途径的平衡可能决定了IL-6对AR反式激活的总体作用。
The effects of IL-6 on prostate cancer cells are well documented yet remain controversial. Some reports suggested that IL-6 could promote prostate cancer cell growth, while others showed that IL-6 could repress prostate cancer cell growth. Here, we systemically examined various IL-6 signaling pathways in prostate cancer cells and found that IL-6 could go through at least three distinct pathways to modulate the functions of androgen receptor (AR), a key transcriptional factor to control the prostate cancer growth. Our results show that IL-6 can enhance AR transactivation via either the STAT3 or MAPK pathways. In contrast, IL-6 can suppress AR transactivation via the PI3K-Akt pathway. Co-existence of these various signaling pathways may result in either additive or conflicting effects on AR transactivation. Together, our results indicate that the balance of these various pathways may then determine the overall effect of IL-6 on AR transactivation.