Involvement of interleukin-6 and androgen receptor signaling in pancreatic cancer.
Involvement of interleukin-6 and androgen receptor signaling in pancreatic cancer.
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DOI：
10.1177/1947601910383417
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发表时间：
2010-08-01
期刊：
影响因子：
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通讯作者：
Yokosuka, Osamu
中科院分区：
文献类型：
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作者：
Okitsu, Kohichiroh;Kanda, Tatsuo;Yokosuka, Osamu
胰腺癌仍然是“难以治疗”的癌症之一。胰腺核受体之一雄激素受体（AR）的信号转导可能与癌变有关。在胰腺癌患者中观察到较高的白细胞介素-6 （IL-6）水平。众所周知，IL-6影响AR信号通路，AR对细胞迁移活动很重要。我们证明IL-6增强STAT3和MAPK的磷酸化，进而增强ar介导的胰腺癌细胞系转录。这种活性被JAK/STAT信号通路的药理抑制剂AG490和MAPK信号通路之一的U0126阻断。IL-6也能在AR存在的情况下促进胰腺癌细胞的迁移，这种活性被AR- sirna阻断。IL-6作为AR信号的正调节因子，为胰腺癌的发生提供了进一步的认识。
Pancreatic cancer remains one of the "difficult-to-treat" cancers. Signaling of androgen receptor (AR), one of the nuclear receptors, in the pancreas may be related to carcinogenesis. Higher interleukin-6 (IL-6) levels have been observed in pancreatic cancer patients. It is also well known that IL-6 affects the AR signaling pathway and that AR is important for cell migration activities. We demonstrated that IL-6 enhances the phosphorylation of STAT3 and MAPK, which in turn enhances AR-mediated transcription in pancreatic cancer cell lines. This activity was blocked by a pharmacological inhibitor of the JAK/STAT signaling pathway, AG490, and one of the MAPK signaling pathways, U0126. IL-6 also enhances pancreatic cancer cell migration in the presence of AR. This activity is blocked by AR-siRNA. IL-6 acts as a positive regulator in AR signaling, providing further insight into the progression of pancreatic carcinogenesis.