title: Differential reactivation of fetal/neonatal genes in mouse liver tumors induced in cirrhotic and non-cirrhotic conditions.
abstract: Hepatocellular carcinoma develops in either chronically injured or seemingly intact livers. To explore the tumorigenic mechanisms underlying these different conditions, we compared the mRNA expression profiles of mouse hepatocellular tumors induced by the repeated injection of CCl4 or a single diethylnitrosamine (DEN) injection using a cDNA microarray. We identified tumor-associated genes that were expressed differentially in the cirrhotic CCl4 model (H19, Igf2, Cbr3, and Krt20) and the non-cirrhotic DEN model (Tff3, Akr1c18, Gpc3, Afp, and Abcd2) as well as genes that were expressed comparably in both models (Ly6d, Slpi, Spink3, Scd2, and Cpe). The levels and patterns of mRNA expression of these genes were validated by quantitative RT-PCR analyses. Most of these genes were highly expressed in mouse livers during the fetal/neonatal periods. We also examined the mRNA expression of these genes in mouse tumors induced by thioacetamide, another cirrhotic inducer, and those that developed spontaneously in non-cirrhotic livers and found that they shared a similar expression profile as that observed in CCl4 -induced and DEN-induced tumors, respectively. There was a close relationship between the expression levels of Igf2 and H19 mRNA, which were activated in the cirrhotic models. Our results show that mouse liver tumors reactivate fetal/neonatal genes, some of which are specific to cirrhotic or non-cirrhotic modes of pathogenesis.
authors.affiliation: Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Kiyonaga
authors.initials: K
authors.lastname: Fujii
authors.affiliation: Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nagahama
authors.affiliation: Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Ooshio
authors.affiliation: Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Bing
authors.initials: B
authors.lastname: Xin
authors.affiliation: Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Division of Gastroenterological and General Surgery, Department of Surgery, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Furukawa
authors.affiliation: Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishikawa
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction
keywords: Hepatocellular carcinoma; insulin-like growth factor 2; liver cirrhosis; mRNA expression; trefoil factor 3