title: Iron overload promotes Cyclin D1 expression and alters cell cycle in mouse hepatocytes.
abstract: OBJECTIVE
  Patients exhibiting hepatic iron overload frequently develop hepatocellular carcinoma. An impaired expression of hepatic genes could be involved in this phenomenon. Our aim was to identify, during iron overload, hepatic genes involved in cell cycle which are misregulated.
  
  
  RESULTS
  Mouse iron overload was obtained by carbonyl-iron supplementation or iron-dextran injection. As expected, liver iron overload was associated to both hepatomegaly and hepatocyte polyploidisation. Hepatic gene expression was investigated using macroarray hybridizations. Cyclin D1 mRNA was the only gene whose expression increased in both models. Its overexpression was confirmed by real-time quantitative PCR. Immunobloting analysis demonstrated a strong increase of Cyclin D1 protein expression in iron-overloaded hepatocytes. This overexpression was correlated with early abnormalities in their cell cycle progression judged, in vitro, on DNA synthesis and mitotic index increase.
  
  
  CONCLUSIONS
  Our data demonstrates that Cyclin D1, a protein involved in G1-phase of cell cycle, is overexpressed in the iron-overloaded liver. This iron-induced expression of Cyclin D1 may contribute to development of cell cycle abnormalities, suggesting a role of Cyclin D1 in iron-related hepatocarcinogenesis.
authors.affiliation: INSERM U522, IFR 140, Université de Rennes 1, F-35033 Rennes, France.
authors.forename: Marie-Bérengère
authors.initials: MB
authors.lastname: Troadec
authors.forename: Brice
authors.initials: B
authors.lastname: Courselaud
authors.forename: Lénaïck
authors.initials: L
authors.lastname: Détivaud
authors.forename: Christelle
authors.initials: C
authors.lastname: Haziza-Pigeon
authors.forename: Patricia
authors.initials: P
authors.lastname: Leroyer
authors.forename: Pierre
authors.initials: P
authors.lastname: Brissot
authors.forename: Olivier
authors.initials: O
authors.lastname: Loréal
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics*; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology*; D019190:Iron Overload / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D019938:Cyclin D1