Proteomic analysis of human thyroid cell lines reveals reduced nuclear localization of Mn-SOD in poorly differentiated thyroid cancer cells
Proteomic analysis of human thyroid cell lines reveals reduced nuclear localization of Mn-SOD in poorly differentiated thyroid cancer cells
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DOI：
10.1007/bf03345356
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发表时间：
2005
影响因子：
5.4
通讯作者：
D. Russo;A. Bisca;M. Celano;F. Talamo;F. Arturi;A. Scipioni;I. Presta;S. Bulotta;E. Ferretti
中科院分区：
文献类型：
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作者：
D. Russo;A. Bisca;M. Celano;F. Talamo;F. Arturi;A. Scipioni;I. Presta;S. Bulotta;E. Ferretti
利用从不同分化程度的肿瘤中获得的人甲状腺细胞系的核提取物之间的差异蛋白质阵列来定义甲状腺肿瘤进展期间发生的分子改变。从分化良好的TPC-1（乳头状癌）和分化不良的ARO（间变性癌）细胞的核提取物显示了一个整体相似的蛋白质表达模式，揭示了通过二维凝胶电泳分析。然而，锰-超氧化物歧化酶（Mn-SOD）被明确确定为显着减少表达ARO相比，TPC-1细胞的质谱程序。通过Western blot和免疫荧光分析证实了Mn-SOD在核区室中的表达减少。免疫组化检测到类似的核锰超氧化物歧化酶的表达模式，在人类甲状腺肿瘤，与最低或不存在的未分化癌的检测。肿瘤细胞核Mn-SOD含量低于正常甲状腺细胞。这些数据表明，Mn-SOD的核表达的改变与抗氧化保护系统的其他元素的变化相平行，在甲状腺肿瘤的进展过程中发生分化的损失。
Differential protein arrays between nuclear extracts of human thyroid cell lines obtained from tumors with different degree of differentiation were exploited to define molecular alterations occurring during thyroid tumor progression. Nuclear extracts from the well differentiated TPC-1 (from papillary carcinoma) and the poorly differentiated ARO (from anaplastic carcinoma) cells showed an overall similar pattern of protein expression as revealed by two-dimensional gel electrophoresis analysis. However, manganese-superoxide dismutase (Mn-SOD) was clearly identified by mass spectrometry procedures as significantly less expressed in ARO compared to TPC-1 cells. A reduced expression of Mn-SOD in the nuclear compartment was confirmed by Western blot and immunofluorescence analysis. A similar expression pattern of nuclear Mn-SOD was detected by immunohistochemistry in human thyroid tumors, with the lowest or absent detection in anaplastic carcinomas. Moreover, the levels of nuclear Mn-SOD in tumor cells were lower than in the normal thyrocytes. These data indicate that an altered nuclear expression of Mn-SOD parallels, together with changes in other elements of the antioxidant protective system, the loss of differentiation occurring during the progression of thyroid tumors.