High mobility group box associated with cell proliferation appears to play an important role in hepatocellular carcinogenesis in rats and humans.
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.
Suzuki
Shugo
S
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
Takeshita
Kentaro
K
Asamoto
Makoto
M
Takahashi
Satoru
S
Kandori
Hitoshi
H
Tsujimura
Kazunari
K
Saito
Fumiyo
F
Masuko
Kazuo
K
Shirai
Tomoyuki
T
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
D006609:High Mobility Group Proteins