...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Cellular Physiology >IL-1 beta induces urokinase-plasminogen activator expression and cell migration through PKC alpha, JNK1/2, and NF-kappaB in A549 cells.
【24h】

IL-1 beta induces urokinase-plasminogen activator expression and cell migration through PKC alpha, JNK1/2, and NF-kappaB in A549 cells.

机译：il - 1β诱发urokinase-plasminogen活化剂通过αPKC表达和细胞迁移,JNK1/2, NF-kappaB A549细胞。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Breakdown of the extracellular matrix (ECM) is accomplished by the concerted action of several proteases, including the urokinase plasminogen-activator (uPA) system and matrix metalloproteinases (MMPs), which is crucial for cancer invasion and metastasis. Several reports have shown that the levels of IL-1 beta and MMPs in plasma of the patients with lung cancer are significantly elevated and link to the invasion of tumor cells. Therefore, we investigated whether IL-1 beta-induced expression of uPA participated in lung cancer progression. In this study, IL-1 beta significantly induced uPA expression and activity via PKC alpha-dependent JNK1/2 and NIK cascades, linking to IKK alpha/beta activation, p65 translocation and transcription activity, using pharmacological inhibitors and transfection with dominant negative mutants and siRNAs. IL-1 beta-induced uPA protein and mRNA expression in a time- and concentration-dependent manner, which was inhibited by pretreatment with the inhibitors of JNK1/2 (SP600125), PKC (Ro31-8220, Go6976), or NF-kappaB (helenalin), and transfection with dominant negative mutants of PKC alpha, NIK, and IKK beta, and siRNAs of JNK1/2 and p65. IL-1 beta stimulated PKC alpha translocation to plasma membrane leading to phosphorylation of JNK1/2, which was attenuated by PKC inhibitors and transfection with shRNAs of JNK1/2, but not by helenalin. In addition, IL-1beta stimulated p65 phosphorylation and translocation into nucleus concomitant with I kappaB alpha phosphorylation and I kappaB alpha degradation, which was mediated via activation of PKC alpha-dependent JNK1/2-NIK/IKK beta cascade. These results demonstrated that in A549 cells, activation of p50/p65 heterodimer through sequential activation of PKC alpha-JNK-NIK-IKK beta-NF-kappaB was required for IL-1 beta-induced uPA expression associated with migration of tumor cells.
机译：细胞外基质(ECM)的崩溃通过一些的协调一致的行动蛋白酶,包括尿激酶纤溶酶原激活物(uPA)系统和矩阵金属蛋白酶(),这是至关重要的癌症入侵和转移。表明,il - 1β和基质金属蛋白酶的水平吗肺癌患者的血浆显著升高和链接到入侵的肿瘤细胞。是否il - 1 beta-induced uPA的表情参与了肺癌进展。研究表明,il - 1β显著诱导uPA通过PKC alpha-dependent表达式和活动JNK1/2尼克瀑布、IKK的链接α/β激活,p65易位转录活性,使用药物抑制剂和转染占主导地位负突变体和siRNAs。uPA蛋白质和mRNA表达,在一个时间浓度的方式,预处理的抑制剂所抑制JNK1/2 (SP600125)、PKC (Ro31-8220、帽子Go6976),还是NF-kappaB (helenalin)和转染显性负突变体的PKCα、尼克和IKKβ,siRNAs JNK1/2 p65。等离子体刺激PKCα易位膜导致JNK1/2的磷酸化,PKC抑制剂和减毒的转染的shrna JNK1/2,但不是helenalin。磷酸化和易位到细胞核与我相伴kappaBα磷酸化和我kappaBα退化,这是通过激活PKC alpha-dependent介导JNK1/2-NIK / IKK beta级联。证明了在A549细胞,激活通过顺序激活p50 / p65异质二聚体的PKC alpha-JNK-NIK-IKK beta-NF-kappaB所需的il - 1 beta-induced uPA表达式与肿瘤细胞的迁移有关。

著录项

相似文献

  • 外文文献
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号