Regulation of iron metabolism-related genes in diethylnitrosamine-induced mouse liver tumors
- Authors
- Youn, Pilju; Kim, Soohee; Ahn, Jin Hee; Kim, Yongbaek; Park, Jung-Duck; Ryu, Doug-Young
- Issue Date
- Feb-2009
- Publisher
- ELSEVIER IRELAND LTD
- Keywords
- Mouse; Liver tumors; Iron metabolism; Ceruloplasmin; DMT1 IRE(+)
- Citation
- TOXICOLOGY LETTERS, v.184, no.3, pp 151 - 158
- Pages
- 8
- Journal Title
- TOXICOLOGY LETTERS
- Volume
- 184
- Number
- 3
- Start Page
- 151
- End Page
- 158
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/23318
- DOI
- 10.1016/j.toxlet.2008.11.002
- ISSN
- 0378-4274
1879-3169
- Abstract
- Background: It has been suggested that the altered iron metabolism in liver tumors, characterized by the iron-deficient phenotype, is of importance for tumor growth. Aim: This study was performed to elucidate the mechanisms underlying iron deficiency in liver tumors by examining how the liver tumor development affects the expression of iron metabolism-related genes. Methods: Iron metabolism reference values were analyzed in the sera of diethylnitrosamine-induced hepatocellular adenoma-bearing mice. Expression of iron metabolism-related genes was analyzed in adenomas and surrounding non-tumor tissues, and a subgroup of adenoma-bearing mice loaded with iron 72 h before sacrifice. Results: Iron content of the adenoma tissues was 2.0-2.5-fold lower compared to surrounding and age-matched control tissues. There was no significant difference in serum iron levels between the adenoma-bearing and control mice, while the adenoma-bearing mice exhibited a 2.4-fold lower level of serum transferrin saturation. Expression of iron metabolism-related genes was dysregulated in the adenomas. Iron loading affected protein expression similarly in the adenomas and surrounding tissues suggesting that iron-responsive regulation of the proteins was not impaired. However, the mRNA expression for ceruloplasmin and divalent metal transporter 1 (DMT1) IRE(+) in the adenomas was altered independently of iron status, and the dysregulation may contribute to diminished iron content. Conclusion: These findings suggest that diethylnitrosamine-induced liver adenoma-bearing mice have abnormal iron metabolism and that dysregulation of iron metabolism-related genes contributes to iron deficiency in the adenomas. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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