Greater expression of transforming growth factor alpha and proliferating cell nuclear antigen staining in mouse hepatoblastomas than hepatocellular carcinomas induced by a diethylnitrosamine-sodium phenobarbital regimen.
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.
Sakairi
T
T
Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., Kisarazu, Chiba, Japan. 4307434@mitsubishi-pharm.co.jp
Kobayashi
K
K
Goto
K
K
Okada
M
M
Kusakabe
M
M
Tsuchiya
T
T
Sugimoto
J
J
Sano
F
F
Mutai
M
M
D000284:Administration, Oral; D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus / Q000737:chemistry / Q000187:drug effects; D003593:Cytoplasm / Q000737:chemistry / Q000187:drug effects; D004052:Diethylnitrosamine / Q000008:administration & dosage / Q000494:pharmacology*; D018197:Hepatoblastoma / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010634:Phenobarbital / Q000008:administration & dosage / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis* / Q000276:immunology; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis* / Q000276:immunology
D018809:Proliferating Cell Nuclear Antigen; D016211:Transforming Growth Factor alpha; D004052:Diethylnitrosamine; D010634:Phenobarbital