title: High mobility group box associated with cell proliferation appears to play an important role in hepatocellular carcinogenesis in rats and humans.
abstract: To identify genes important in hepatocellular carcinogenesis, especially processes involved in malignant transformation, we focused on differences in gene expression between adenomas and carcinomas by DNA microarray. Eighty-one genes for which expression was specific in carcinomas were analyzed using Ingenuity Pathway Analysis software and Gene Ontology, and found to be associated with TP53 and regulators of cell proliferation. In the genes associated with TP53, we selected high mobility group box (HMGB) for detailed analysis. Immunohistochemistry revealed expression of HMGBs in carcinomas to be significantly higher than in other lesions among both human and rat liver, and a positive correlation between HMGBs and TP53 was detected in rat carcinomas. Knock-down of HMGB 2 expression in a rat hepatocellular carcinoma cell line by RNAi resulted in inhibition of cell growth, although no effects on invasion were evident in vitro. These results suggest that acquisition of malignant potential in the liver requires specific signaling pathways related to high cell proliferation associated with TP53. In particular, HMGBs appear to have an important role for progression and cell proliferation associated with loss of TP53 function in rat and in human hepatocarcinogenesis.
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Nagoya 467-8601, Aichi, Japan. shugo@med.nagoya-cu.ac.jp
authors.forename: Shugo
authors.initials: S
authors.lastname: Suzuki
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takeshita
authors.forename: Makoto
authors.initials: M
authors.lastname: Asamoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kandori
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tsujimura
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Saito
authors.forename: Kazuo
authors.initials: K
authors.lastname: Masuko
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirai
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000503:physiopathology*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006609:High Mobility Group Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D006609:High Mobility Group Proteins