Expression of peroxiredoxin and thioredoxin in human lung cancer and paired normal lung

Expression of peroxiredoxin and thioredoxin in human lung cancer and paired normal lung
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DOI:
10.1111/j.1440-1843.2006.00849.x
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发表时间:
2006-05-01
期刊:
影响因子:
6.9
通讯作者:
Hwang, SC
Hwang, SC
中科院分区:
医学2区
文献类型:
--
作者:
Park, JH;Kim, YS;Hwang, SC

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背景资料:过氧化物酶(Peroxiredoxins,Prxs)参与细胞增殖、分化和凋亡等多种细胞过程的调控。然而,Prx蛋白的病理生理学意义,特别是在肺部疾病中,尚未确定。因此,作者研究了各种Prx亚型在肺癌中的分布和表达,并与正常肺从人类和mouse.Methods:诊断为肺癌谁接受手术在Ajou医疗中心的患者进行了登记。通过蛋白质组学技术分析Prxs、硫氧还蛋白和硫氧还蛋白还原酶的表达。结果:免疫组织化学染色显示Prx Ⅰ、Ⅱ、Ⅲ、Ⅴ亚型主要表达于正常小鼠支气管上皮、肺泡上皮和肺泡巨噬细胞。与正常肺组织相比,亚型I、III和硫氧还蛋白在肺癌组织中过表达。也有一个增加量的氧化形式的Prx我和一个假定的截短形式的Prx III在肺癌样本中进行分析时,在二维电泳。此外,在肺癌患者的组织提取物中,在一维电泳上存在40-kDa的中等分子量蛋白带和超过20 kDa的高分子量蛋白带,其被抗Prx(a-Prx)I抗体识别。Prx I的上调,肺癌组织中的Prx III和硫氧还蛋白可能代表肿瘤细胞试图以有利于生存的方式适应微环境和扩散。
Background: Peroxiredoxins (Prxs) have been implicated in regulating many cellular processes including cell proliferation, differentiation and apoptosis. However, the pathophysiological significance of Prx proteins, especially in lung disease, has not been defined. Therefore, the authors investigated the distribution and expression of various Prx isoforms in lung cancer and compared this with normal lung from human and mouse.Methods: Patients diagnosed with lung cancer who underwent surgery at Ajou Medical Center were enrolled. Expression of Prxs, thioredoxin and thioredoxin reductase was analysed by proteomic techniques. Immunohistochemistry was performed to localize Prx proteins.Results: Immunohistochemical staining showed that the isoforms of Prx I, II, III and V were predominantly expressed in bronchial and alveolar epithelium as well as in alveolar macrophages of the normal mouse lung. The isoforms I, III and thioredoxin were overexpressed in lung cancer tissues compared with normal lungs. There was also an increased amount of oxidized form of Prx I and a putative truncated form of Prx III in lung cancer samples when analysed on two-dimensional electrophoresis. In addition, a 40-kDa intermediate MW protein band and high MW bands of over 20 kDa, recognized by anti-Prx (a-Prx) I antibody, were present in tissue extracts of lung cancer patients on one-dimensional electrophoresis.Conclusion: The upregulation of Prx I, Prx III and thioredoxin in lung cancer tissue may represent an attempt by tumour cells to adjust to the microenvironment in a manner that is advantageous to survival and proliferation.