Regulation of iron metabolism-related genes in diethylnitrosamine-induced mouse liver tumors

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Youn, Pilju; Kim, Soohee; Ahn, Jin Hee; Kim, Yongbaek; Park, Jung-Duck; Ryu, Doug Young
Issue Date
Toxicol. Lett. 184, 151-158
MouseLiver tumorsIron metabolismCeruloplasminDMT1 IRE(+)
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 agematched
control tissues. There was no significant difference in serum iron levels between the adenomabearing
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 divalentmetal transporter 1 (DMT1) IRE(+) in the adenomaswas alteredindependently
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.
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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