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

Abstract

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 downregulated 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.

• Authors: Kerstin Dallmann, Heike Junker, Stefan Balabanov, Uwe Zimmermann, Jürgen Giebel, Reinhard Walther
• Journal: International journal of cancer (Int J Cancer) Vol. 108 Issue 3 Pg. 342-7 (Jan 20 2004) ISSN: 0020-7136 [Print] United States
• PMID: 14648699 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright 2003 Wiley-Liss, Inc.

Chemical References

• RNA, Messenger
• Ureohydrolases
• AGMAT protein, human
• agmatinase

Topics

• Adenocarcinoma, Clear Cell (enzymology, pathology)
• Animals
• Blotting, Northern
• COS Cells
• Carcinoma, Renal Cell (enzymology)
• Chlorocebus aethiops
• Down-Regulation
• Electrophoresis, Gel, Two-Dimensional
• Gene Expression Regulation, Enzymologic
• Humans
• Kidney (enzymology)
• Kidney Neoplasms (enzymology, pathology)
• Mitochondria (enzymology)
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured
• Ureohydrolases (genetics, metabolism)