Human agmatinase is diminished in the clear cell type of renal cell carcinoma

被引:52
作者
Dallmann, K
Junker, H
Balabanov, S
Zimmermann, U
Giebel, J
Walther, R
机构
[1] Ernst Moritz Arndt Univ Greifswald, Dept Med Biochem & Mol Biol, Greifswald, Germany
[2] Ernst Moritz Arndt Univ Greifswald, Dept Urol, Greifswald, Germany
[3] Ernst Moritz Arndt Univ Greifswald, Dept Anat, Greifswald, Germany
关键词
renal cell carcinoma; agmatinase; 2D-PAGE; kidney; proteome; arginine metabolism; nitric oxide; polyamine;
D O I
10.1002/ijc.11459
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The proteome of RCC was analyzed by 2D PAGE to search for tumor-associated proteins. Agmatinase, which hydrolyzes agmatine to putrescine and urea, was identified by mass spectrometry and database searches and shown to be down-regulated in tumor cells. Additionally, RT-PCR and Northern blot analyses demonstrated a clearly decreased amount of agmatinase mRNA in tumor cells. The differential expression of agmatinase mRNA was confirmed at the protein level. Western blot analysis showed almost no detectable agmatinase protein in tumor cells compared to corresponding normal renal tissue. Agmatinase mRNA is most abundant in human liver and kidney but expressed to a lesser extent in several other tissues, including skeletal muscle and small intestine. The human agmatinase gene encodes a 352-residue protein with a putative mitochondrial targeting sequence at the N-terminus. Using transfection and immunohistochemical studies, we show that agmatinase is localized in the mitochondria. Immunohistochemical studies revealed that agmatinase in the normal kidney is restricted to tubulus epithelial cells, while in tumors staining was low and heterogeneous. Thus, expression of human agmatinase is altered in RCC. We discuss the consequences of these findings in terms of polyamine, NO metabolism and macrophage function. (C) 2003 Wiley-Liss, Inc.
引用
收藏
页码:342 / 347
页数:6
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