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Notch-1 signaling facilitates survivin expression in human non-small cell lung cancer cells
Chen, Yuqing ; Li, Dianming ; Liu, Hongli ; Xu, Huanbai ; Zheng, Honghua ; Qian, Feng ; Li, Wei ; Zhao, Chengling ; Wang, Zhenhuan ; Wang, Xiaojing ; Zheng HH(郑红花)
刊名http://dx.doi.org/10.4161/cbt.11.1.13730
2011
关键词MAMMALIAN NOTCH HYPOXIA INHIBITION PATHWAY APOPTOSIS TARGET CHEMOSENSITIVITY ADENOCARCINOMA SENSITIVITY INVASION
英文摘要The oncogenic potential of Notch activation is observed in many instances including lung tumorigenesis, but the associated molecular regulatory mechanism has not been thoroughly defined. It has been demonstrated that hypoxia can act as one of the major stimuli in the progression of many types of tumorigenesis. This study was designed to examine the activation of Notch-1 signaling by hypoxia and its contribution to survivin expression in human lung carcinomas. Western-blot and PCR analysis showed that Notch-1 signaling is activated by hypoxia in the human non-small cell lung cancer (NSCLC) cell line, A549, through the upregulation of Notch-1, along with its intracellular domain (N1ICD). The activity of Hes-1, a crucial target molecule of N1ICD, was also increased under hypoxia. Interestingly, blockade of the Notch-1 pathway by a gamma-secretase inhibitor or small interfering RNA (siRNA) inhibited survivin expression. Conversely, activation of Notch-1 signaling by N1ICD or stimulation with the Jagged1 ligand enhanced survivin levels in A549 cells. Notably, HIF-1 alpha cooperated with Notch-1 signaling to increase survivin expression through its direct association with N1ICD, consequently accelerating survivin transcription. Overall, our findings suggest that Notch-1 signaling is involved in the upregulation of survivin expression in lung cancer cells, which is synergized by HIF-1 alpha.
语种英语
出版者CANCER BIOL THER
内容类型期刊论文
源URL[http://dspace.xmu.edu.cn/handle/2288/93321]  
专题医学院-已发表论文
推荐引用方式
GB/T 7714
Chen, Yuqing,Li, Dianming,Liu, Hongli,et al. Notch-1 signaling facilitates survivin expression in human non-small cell lung cancer cells[J]. http://dx.doi.org/10.4161/cbt.11.1.13730,2011.
APA Chen, Yuqing.,Li, Dianming.,Liu, Hongli.,Xu, Huanbai.,Zheng, Honghua.,...&郑红花.(2011).Notch-1 signaling facilitates survivin expression in human non-small cell lung cancer cells.http://dx.doi.org/10.4161/cbt.11.1.13730.
MLA Chen, Yuqing,et al."Notch-1 signaling facilitates survivin expression in human non-small cell lung cancer cells".http://dx.doi.org/10.4161/cbt.11.1.13730 (2011).
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