Profilin 1 overexpression in renal cell carcinoma

Profilin 1 overexpression in renal cell carcinoma
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DOI:
10.1111/j.1442-2042.2010.02670.x
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发表时间:
2011-01-01
影响因子:
2.6
通讯作者:
Baba, Shiro
Baba, Shiro
中科院分区:
医学3区
文献类型:
--
作者:
Minamida, Satoru;Iwamura, Masatsugu;Baba, Shiro

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目的:应用化学蛋白质组学方法研究肾细胞癌(RCC)中高表达抗原的表达。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)和串联质谱(LC-MS/MS)对培养上清中的蛋白质进行检测。结果:筛选出4个差异表达蛋白(profilin 1,amyloid beta A4 protein [APP],proprotein convertase subtilisin/kexin type 1 inhibitor [ProSAAS],galectin-3-binding protein [LGALS 3BP])。这些在正常肾组织中没有过度表达,在RCC中也没有报道。通过蛋白质印迹法检测正常肾组织和RCC组织中它们的水平。APP、ProSAAS和LGALS 3BP在肾细胞癌和正常肾组织中的表达水平无差异。Profilin 1在肾细胞癌组织中呈高表达。在此观察的基础上,进行了profilin 1在正常肾脏和RCC组织中的免疫组化分析。在正常组织中,作为RCC来源的小管对profilin 1染色呈阳性。结论:Profilin 1在肾细胞癌的发生、发展过程中起重要作用。因此,它有可能作为RCC的诊断或进展生物标志物和治疗靶点。
Objectives:To gain information about overexpressed antigens in renal cell carcinoma (RCC) by using a chemical proteomics approach.Methods:RCC cell line 769P was cultured and proteome analysis was subsequently carried out in the culture supernatants. By using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and tandem mass spectrometry (LC-MS/MS), proteins in the culture supernatants were searched. A MEDLINE search to define the functions of the identified proteins was carried out.Results:Four differentially regulated proteins (profilin 1, amyloid beta A4 protein [APP], proprotein convertase subtilisin/kexin type 1 inhibitor [ProSAAS], galectin-3-binding protein [LGALS3BP]) were selected. These were not overexpressed in normal kidney tissue or reported in RCC. Their levels were measured through western blotting of normal kidney and RCC tissues. No differences were observed in the expression levels of APP, ProSAAS or LGALS3BP between RCC and normal kidney tissues. Profilin 1 was overexpressed in RCC tissue. On the basis of this observation, an immunohistochemical analysis of profilin 1 in normal kidney and RCC tissues was carried out. In normal tissues, tubules that were sources of RCC stained positive for profilin 1. In RCC tissue, in contrast, the stromal cells in the tumors stained positive.Conclusions:Profilin 1 can be a key element in the pathological processes of RCC, such as tumorigenesis and/or tumor growth. Thus, it has the potential to serve as a diagnostic or progression biomarker and therapeutic target in RCC.