iASPP is over-expressed in human non-small cell lung cancer and regulates the proliferation of lung cancer cells through a p53 associated pathway.
iASPP is over-expressed in human non-small cell lung cancer and regulates the proliferation of lung cancer cells through a p53 associated pathway.
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DOI：
10.1186/1471-2407-10-694
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发表时间：
2010-12-30
期刊：
影响因子：
3.8
通讯作者：
Jiang WG
中科院分区：
文献类型：
--
作者：
Chen J;Xie F;Zhang L;Jiang WG
iASPP是肿瘤抑制因子p53的关键抑制剂，并发现在某些恶性疾病中上调。本研究调查了iASPP在临床肺癌（世界上主要的癌症类型）中的表达，以及该分子对肺癌细胞的生物学影响。使用免疫组织化学方法评估肺癌组织中的iASPP蛋白水平。在体外，用慢病毒介导的shRNA方法抑制iASPP基因表达，并研究敲低iASSP对肺癌细胞系的生物学影响与p53表达状态的关系。我们发现iASPP在肺癌组织中的表达显著高于癌旁正常组织。iASPP shRNA处理导致肺癌细胞中iASPP的下调。随后，两种肺肿瘤细胞系A459和95D的细胞增殖减少，这两种细胞系均具有野生型p53表达。相比之下，H1229细胞中iASPP的减少对其生长速率没有影响，H1229细胞是一种几乎没有p53表达的细胞。iASPP调节肺癌细胞的增殖和运动。这种作用与p53通路密切相关。结合iASPP在临床肺癌中的表达模式，认为iASPP在肺癌的发生发展中起着重要作用，是肺癌治疗的潜在靶点。
iASPP is a key inhibitor of tumour suppressor p53 and is found to be up-regulated in certain malignant conditions. The present study investigated the expression of iASPP in clinical lung cancer, a leading cancer type in the world, and the biological impact of this molecule on lung cancer cells. iASPP protein levels in lung cancer tissues were evaluated using an immunohistochemical method. In vitro, iASPP gene expression was suppressed with a lentvirus-mediated shRNA method and the biological impact after knocking down iASSP on lung cancer cell lines was investigated in connection with the p53 expression status. We showed here that the expression of iASPP was significantly higher in lung cancer tissues compared with the adjacent normal tissues. iASPP shRNA treatment resulted in a down-regulation of iASPP in lung cancer cells. There was a subsequent reduction of cell proliferation of the two lung tumour cell lines A459 and 95D both of which had wild-type p53 expression. In contrast, reduction of iASPP in H1229 cells, a cell with little p53 expression, had no impact on its growth rate. iASPP regulates the proliferation and motility of lung cancer cells. This effect is intimately associated with the p53 pathway. Together with the pattern of the over-expression in clinical lung cancers, it is concluded that iASPP plays an pivotal role in the progression of lung cancer and is a potential target for lung cancer therapy.
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