Abstract
Transforming growth factor alpha (TGF-alpha) is a potent stimulator of normal hepatocyte proliferation, considered to have relationship to the liver regeneration or carcinogenesis. In this study, we investigated immunohistochemically the association between expression of TGF-alpha and cell proliferation activity in mouse hepatoblastomas (HBs) and hepatocellular carcinomas (HCCs) induced in B6C3F1 mice by diethylnitrosamine and sodium phenobarbital. The TGF-alpha-positive rate in HBs (29.2%) was significantly higher than that in HCCs (12.7%). Likewise, the proliferating cell nuclear antigen-positive rate (22.2%) was higher than the HCC value (14.5%). On the individual data for both TGF-alpha and PCNA, most of the HBs showed higher positive rates than HCCs. In HBs, TGF-alpha was localized only in the nuclei, whereas some HCC cells stained positive both in their nuclei and cytoplasm (0.6%). These results suggest expression of TGF-alpha and its localization might be linked to cell proliferation and play a role in malignant progression of mouse HBs.
MeSH terms
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Administration, Oral
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Animals
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Carcinogenicity Tests / methods
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Carcinoma, Hepatocellular / chemically induced
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Carcinoma, Hepatocellular / metabolism*
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Carcinoma, Hepatocellular / pathology
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Cell Division / physiology
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Cell Nucleus / chemistry
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Cell Nucleus / drug effects
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Cytoplasm / chemistry
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Cytoplasm / drug effects
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Diethylnitrosamine / administration & dosage
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Diethylnitrosamine / pharmacology*
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Hepatoblastoma / chemically induced
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Hepatoblastoma / metabolism*
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Hepatoblastoma / pathology
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Immunohistochemistry
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Liver Neoplasms, Experimental / chemically induced
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Liver Neoplasms, Experimental / metabolism*
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Liver Neoplasms, Experimental / pathology
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Male
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Mice
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Mice, Inbred Strains
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Phenobarbital / administration & dosage
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Phenobarbital / pharmacology*
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Proliferating Cell Nuclear Antigen / analysis*
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Proliferating Cell Nuclear Antigen / immunology
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Time Factors
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Transforming Growth Factor alpha / biosynthesis*
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Transforming Growth Factor alpha / immunology
Substances
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Proliferating Cell Nuclear Antigen
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Transforming Growth Factor alpha
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Diethylnitrosamine
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Phenobarbital