IL-6 stimulates STAT3 and Pim-1 kinase in pancreatic cancer cell lines.
IL-6 stimulates STAT3 and Pim-1 kinase in pancreatic cancer cell lines.
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IL-6 刺激胰腺癌细胞系中的 STAT3 和 Pim-1 激酶。
DOI：
10.1097/mpa.0b013e31823cdd10
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发表时间：
2012-07
期刊：
影响因子：
2.9
通讯作者：
Baker AF
中科院分区：
文献类型：
--
作者：
Block KM;Hanke NT;Maine EA;Baker AF
我们研究了白细胞介素6(IL-6)激活的胰腺细胞信号转导和转录激活因子3(STAT3)和原癌基因丝氨酸/苏氨酸蛋白(Pim-1)激酶。Western blotting检测IL-6受体(IL-6R)的表达及IL-6诱导的细胞信号转导。葫芦素I被用作药理学工具来研究STAT3在Pim-1激活中的作用。稳定过表达Pim-1激酶细胞系的特征是它们对IL-6的体外反应，以及它们作为SCID小鼠侧翼肿瘤的生长速度。IL-6R在多种癌细胞系中均有表达。在PANC-1细胞中，IL-6处理增加了P-STAT3和Pim-1激酶的表达。葫芦素I单独处理可增加野生型和Pim-1过表达细胞中pErk1/2的表达，并导致对照和IL-6刺激的细胞中Pim-1蛋白水平升高，提示Pim-1的上调可能部分不依赖于STAT3。PIM-1过表达对PANC-1或MiaPaCa2细胞的体外和体内生长无明显影响。IL-6在胰腺癌细胞系模型中激活STAT3并刺激Pim-1激酶。Pim-1表达的调节和结果似乎高度依赖于上下文。
We investigated the signaling pathways activated in response to Interleukin (IL-6) in pancreatic cell lines, with a focus on signal transducer and activator of transcription 3 (STAT3) and proto-oncogene serine/threonine-protein (Pim-1) kinase. IL-6 receptor (IL-6R) expression and IL-6 induced cell signaling was measured by Western blotting in human pancreatic cell lines. Cucurbitacin I was used as a pharmacological tool to investigate the role of STAT3 in Pim-1 activation. Stably over-expressing Pim-1 kinase cell lines were characterized for their response to IL-6 in vitro, and for their growth rate as flank tumors in scid mice. IL-6R was expressed across multiple cancer cell lines. In Panc-1 cells, IL-6 treatment increased expression of P-STAT3 and Pim-1 kinase. Cucurbitacin I treatment alone increased pErk1/2 expression in wild-type and Pim-1 over-expressing cell lines and resulted in exaggerated Pim-1 kinase protein levels in control and IL-6 stimulated cells, suggesting upregulation of Pim-1 may be partially STAT3 independent. Pim-1 over-expression did not significantly impact growth rate in vitro or in vivo in Panc-1 or MiaPaCa2 cell lines. IL-6 activates STAT3 and stimulates Pim-1 kinase in pancreatic cell line models. The regulation and consequence of Pim-1 expression appears to be highly context dependent.