title: Immunohistochemical localization of transforming growth factor alpha in chemically induced rat hepatocellular carcinomas with reference to differentiation and proliferation.
abstract: Hepatocellular carcinomas (HCCs) were induced in male Fischer 344 rats with dietary 3'-methyl-4-(dimethylamino)-azobenzene treatment and were classified into solid, glandular (well- or poorly differentiated), and trabecular types. Investigation of cell proliferation kinetics and immunohistochemical localization of transforming growth factor alpha (TGF-alpha) demonstrated all solid (n = 24) and poorly differentiated glandular type (n = 6) HCCs to have TGF-alpha-positive nuclei. Nuclear staining of TGF-alpha was also observed in 13 of 28 (46%) trabecular-type HCCs, whereas 12 (43%) exhibited cytoplasmic staining, and 3 (11%) were negative. As for well-differentiated glandular HCCs, 7 of 20 (35%) were positively stained in their nucleus, another 7 (35%) demonstrated antibody binding in the cytoplasm, and 6 (30%) were negative. The order for growth rate evaluated by bromodeoxyuridine (BrdU) labeling was solid (38.22%), poorly differentiated glandular (26.82%), trabecular (7.98%), and well-differentiated glandular (2.57%) types. For trabecular HCCs with nuclear, cytoplasmic, or negative TGF reactions, values were 13.39% (n = 13), 3.61% (n = 12), and 2.01% (n = 3), respectively. Likewise, BrdU-labeling indices for the counterpart groups of well-differentiated glandular type HCCs were 4.53, 1.91, and 1.29%, respectively. The results indicate that TGF-alpha expression might be linked to histopathological differentiation and cell proliferation in rat HCCs.
authors.affiliation: Pharmacokinetics & Toxicology Laboratory, Yokohama Research Center, Mitsubishi-Tokyo Pharmaceuticals Inc, Yokohama, Japan. 1703523@mitsubishi-pharm.co.jp
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Kusakabe
authors.forename: M
authors.initials: M
authors.lastname: Okada
authors.forename: T
authors.initials: T
authors.lastname: Sakairi
authors.forename: K
authors.initials: K
authors.lastname: Goto
authors.forename: T
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: J
authors.initials: J
authors.lastname: Sugimoto
authors.forename: F
authors.initials: F
authors.lastname: Sano
authors.forename: M
authors.initials: M
authors.lastname: Mutai
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000737:chemistry; D002454:Cell Differentiation; D002455:Cell Division; D002467:Cell Nucleus / Q000737:chemistry / Q000187:drug effects; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008749:Methyldimethylaminoazobenzene / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D016211:Transforming Growth Factor alpha / Q000276:immunology / Q000378:metabolism*
chemical_list: D016211:Transforming Growth Factor alpha; D008749:Methyldimethylaminoazobenzene; D001973:Bromodeoxyuridine