title: Regulation of iron metabolism-related genes in diethylnitrosamine-induced mouse liver tumors.
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.
  
  
  OBJECTIVE
  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 72h 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: College of Veterinary Medicine, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Pilju
authors.initials: P
authors.lastname: Youn
authors.forename: Soohee
authors.initials: S
authors.lastname: Kim
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Ahn
authors.forename: Yongbaek
authors.initials: Y
authors.lastname: Kim
authors.forename: Jung-Duck
authors.initials: JD
authors.lastname: Park
authors.forename: Doug-Young
authors.initials: DY
authors.lastname: Ryu
mesh_terms: D018248:Adenoma, Liver Cell / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002570:Ceruloplasmin / Q000235:genetics / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D004052:Diethylnitrosamine; D005293:Ferritins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D064451:Hepcidins; D015151:Immunoblotting; D007279:Injections, Subcutaneous; D007501:Iron / Q000097:blood / Q000378:metabolism*; D007505:Iron-Dextran Complex / Q000008:administration & dosage; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014168:Transferrin / Q000378:metabolism; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D002570:Ceruloplasmin; D003300:Copper; D004052:Diethylnitrosamine; D005293:Ferritins; D064451:Hepcidins; D007501:Iron; D007505:Iron-Dextran Complex; D012333:RNA, Messenger; D014168:Transferrin; D000099236:Solute Carrier Family 11, Member 2