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Greater Expression of Transforming Growth Factor and Proliferating Cell Nuclear Antigen Staining in Mouse Hepatoblastomas Than Hepatocellular Carcinomas Induced by a Diethylnitrosamine-Sodium Phenobarbital Regimen

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan, 4307434{at}mitsubishi-pharm.co.jp

Kiyoshi Kobayashi

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan

Kazuhiro Goto

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan

Miyoko Okada

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan

Manami Kusakabe

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan

Takayuki Tsuchiya

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan

Jiro Sugimoto

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan

Fumiko Sano

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan

Mamoru Mutai

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan

Transforming growth factor (TGF-) 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- and cell proliferation activity in mouse hepatoblastoma s (HBs) and hepatocellular carcinomas (HCCs) induced in B6C3F1 mice by diethylnitrosamine and sodium phenobarbital. The TGF--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- and PCNA, most of the HBs showed higher positive rates than HCCs. In HBs, TGF- 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- and its localization might be linked to cell proliferation and play a role in malignant progression of mouse HBs.

Key Words: B6C3F1 mice • cell proliferation • hepatoblastoma • immunohistochemistry • liver • transforming growth factor .

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				Y. Kim, R. C. Sills, and C. D. Houle Overview of the Molecular Biology of Hepatocellular Neoplasms and Hepatoblastomas of the Mouse Liver Toxicol Pathol, January 1, 2005; 33(1): 175 - 180. [Abstract] [Full Text] [PDF]