The Expression of RNA-Binding Protein HuR in Non-Small Cell Lung Cancer Correlates with Vascular Endothelial Growth Factor-C Expression and Lymph Node Metastasis
The Expression of RNA-Binding Protein HuR in Non-Small Cell Lung Cancer Correlates with Vascular Endothelial Growth Factor-C Expression and Lymph Node Metastasis
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DOI：
10.1159/000216837
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发表时间：
2009-01-01
期刊：
影响因子：
3.5
通讯作者：
Chen, Zhengtang
中科院分区：
文献类型：
--
作者：
Wang, Jun;Zhao, Weipeng;Chen, Zhengtang
应用免疫组织化学方法检测了81例非小细胞肺癌（NSCLC）和15例肺良性病变组织中RNA结合蛋白Hu抗原（HuR）和血管内皮生长因子-C（VEGF-C）的表达水平。HuR在82.7%（67/81）的NSCLC组织中表达。HuR在非小细胞肺癌组织中的阳性表达率为45.7%（37/81），而在良性肺组织中仅有13.3%（2/15）的HuR在细胞核中表达。VEGF-C阳性表达率为70.4%（57/81）。在人NSCLC样本中，胞质而非核HuR表达与VEGF-C水平升高和临床病理变量（包括高肿瘤分级、低分化和淋巴结转移）显著相关。在体外，HuR在刘易斯肺癌细胞中显示出主要的核染色，如通过共聚焦显微镜所见。当肺癌细胞用靶向HuR的siRNA处理时，HuR和VEGF-C蛋白的表达水平显著降低，如通过Western印迹所见。我们的研究结果表明，在NSCLC的一个子集中，存在mRNA稳定因子HuR的细胞分布失调。检测NSCLC组织中胞浆HuR的表达对判断淋巴结转移有重要价值，因为HuR可能是调节VEGF-C表达的重要介质。版权所有（C）2009 S. Karger AG，巴塞尔
The expression levels of the RNA-binding protein Hu antigen (HuR) and vascular endothelial growth factor-C (VEGF-C) were examined immunohistochemically in 81 non-small cell lung cancers (NSCLC) and 15 benign human lung tissues. HuR showed a nuclear overexpression in 82.7% (67/81) of NSCLC specimens. Cytoplasmic immunoreactivity for HuR was observed in 45.7% (37/81) of NSCLC, while only nuclear expression of HuR was observed in 13.3% (2/15) of benign lung tissues. The expression of VEGF-C was present in a subgroup of 70.4% (57/81) of tumor cases. In the human NSCLC samples, cytoplasmic but not nuclear HuR expression was significantly associated with increased levels of VEGF-C and with clinicopathological variables, including high tumor grade, poor differentiation and lymph node metastasis. In vitro, HuR showed a predominantly nuclear staining in Lewis lung cancer cells, as seen by confocal microscopy. When lung cancer cells were treated with siRNA targeted against HuR, expression levels of the HuR and VEGF-C proteins were significantly reduced, as seen by Western blotting. Our findings indicate that there is a dysregulation of the cellular distribution of the mRNA stability factor HuR in a subset of NSCLC. Examination of cytoplasmic HuR in NSCLC tissues will allow for valuable prognostic diagnosis of lymph node metastasis, as HuR might be an important mediator regulating the expression of VEGF-C. Copyright (C) 2009 S. Karger AG, Basel