The prolyl isomerase Pin1 regulates the NF-kappaB signaling pathway and interleukin-8 expression in glioblastoma.
The prolyl isomerase Pin1 regulates the NF-kappaB signaling pathway and interleukin-8 expression in glioblastoma.
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DOI：
10.1038/onc.2009.232
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发表时间：
2009-10-22
期刊：
影响因子：
8
通讯作者：
Benveniste EN
中科院分区：
文献类型：
--
作者：
Atkinson GP;Nozell SE;Harrison DK;Stonecypher MS;Chen D;Benveniste EN
脑肿瘤胶质母细胞瘤仍然是最具侵略性和破坏性的肿瘤之一，尽管几十年来一直在努力寻找更有效的治疗方法。胶质母细胞瘤的标志是NF-κB信号通路的组成性激活，其调节细胞增殖、炎症、迁移和凋亡。已发现脯氨酰异构酶Pin 1直接与NF-κB蛋白p65结合，并导致乳腺癌模型中NF-κB启动子活性增加。我们现在提出的证据表明，这种相互作用发生在胶质母细胞瘤，它有重要的后果NF-κB信号。我们证明，Pin 1水平在原发性胶质母细胞瘤组织中与对照组相比增强，并且Pin 1表达的这种差异影响胶质母细胞瘤衍生细胞的迁移能力。Pin 1敲低降低了细胞核中活化的磷酸化p65的量，导致IL-8基因的转录程序的抑制。通过使用微阵列，我们还观察到其他NF-κB调控基因的表达水平的变化，由于Pin 1敲低。综上所述，这些数据表明Pin 1是胶质母细胞瘤中NF-κB的重要调节因子，并支持将来使用Pin 1作为治疗靶点的概念。
The brain tumor glioblastoma remains one of the most aggressive and devastating tumors despite decades of effort to find more effective treatments. A hallmark of glioblastoma is the constitutive activation of the NF-κB signaling pathway, which regulates cell proliferation, inflammation, migration, and apoptosis. The prolyl isomerase Pin1 has been found to bind directly to the NF-κB protein, p65, and cause increases in NF-κB promoter activity in a breast cancer model. We now present evidence that this interaction occurs in glioblastoma and that it has important consequences on NF-κB signaling. We demonstrate that Pin1 levels are enhanced in primary glioblastoma tissues compared to controls, and that this difference in Pin1 expression affects the migratory capacity of glioblastoma-derived cells. Pin1 knockdown decreases the amount of activated, phosphorylated p65 in the nucleus, resulting in inhibition of the transcriptional program of the IL-8 gene. Through the use of microarray, we also observed changes in the expression levels of other NF-κB regulated genes due to Pin1 knockdown. Taken together, these data suggest that Pin1 is an important regulator of NF-κB in glioblastoma, and support the notion of using Pin1 as a therapeutic target in the future.
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影响因子：
4.8
作者：
Harant, H;deMartin, R;Lindley, IJD
通讯作者：
Lindley, IJD
影响因子：
6
作者：
Bao, L;Kimzey, A;Wang, DG
通讯作者：
Wang, DG
DOI：
10.1158/1078-0432.ccr-08-0618
发表时间：
2008-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Brantley EC;Nabors LB;Gillespie GY;Choi YH;Palmer CA;Harrison K;Roarty K;Benveniste EN
通讯作者：
Benveniste EN
影响因子：
64.8
作者：
Garkavtsev, I;Kozin, SV;Jain, RK
通讯作者：
Jain, RK
DOI：
10.1073/pnas.0604800103
发表时间：
2006-12-05
影响因子：
11.1
作者：
Choi, Youn-Hee;Bernardi, Rosa;Benveniste, Etty N.
通讯作者：
Benveniste, Etty N.