title: Hepatocyte iron loading capacity is associated with differentiation and repression of motility in the HepaRG cell line.
abstract: High liver iron content is a risk factor for developing hepatocellular carcinoma (HCC). However, HCC cells are always iron-poor. Therefore, an association between hepatocyte iron storage capacity and differentiation is suggested. To characterize biological processes involved in iron loading capacity, we used a cDNA microarray to study the differentiation of the human HepaRG cell line, from undifferentiated proliferative cells to hepatocyte differentiated cells. We were able to identify genes modulated along HepaRG differentiation, leading us to propose new genes not previously associated with HCC. Moreover, using Gene Ontology annotations, we demonstrated that HepaRG hepatocyte iron loading capacity occurred both with the repression of genes involved in cell motility, signal transduction, and biosynthesis and with the appearance of genes linked to lipid metabolism and immune response. These results provide new insights in the understanding of the relationship between iron and hepatocyte differentiation during iron-related hepatic diseases.
authors.affiliation: INSERM U522, IFR 140, University of Rennes 1, CHRU Pontchaillou, 35033 Rennes Cedex, France.
authors.forename: Marie-Bérengère
authors.initials: MB
authors.lastname: Troadec
authors.forename: Denise
authors.initials: D
authors.lastname: Glaise
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lamirault
authors.forename: Martine
authors.initials: M
authors.lastname: Le Cunff
authors.forename: Emilie
authors.initials: E
authors.lastname: Guérin
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Le Meur
authors.forename: Lénaïck
authors.initials: L
authors.lastname: Détivaud
authors.forename: Pierre
authors.initials: P
authors.lastname: Zindy
authors.forename: Patricia
authors.initials: P
authors.lastname: Leroyer
authors.forename: Isabelle
authors.initials: I
authors.lastname: Guisle
authors.forename: Hélène
authors.initials: H
authors.lastname: Duval
authors.forename: Philippe
authors.initials: P
authors.lastname: Gripon
authors.forename: Nathalie
authors.initials: N
authors.lastname: Théret
authors.forename: Karim
authors.initials: K
authors.lastname: Boudjema
authors.forename: Christiane
authors.initials: C
authors.lastname: Guguen-Guillouzo
authors.forename: Pierre
authors.initials: P
authors.lastname: Brissot
authors.forename: Jean J
authors.initials: JJ
authors.lastname: Léger
authors.forename: Olivier
authors.initials: O
authors.lastname: Loréal
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012307:Risk Factors
chemical_list: D007501:Iron