Analysis of insulin-like growth factor II (IGF-II) expression in neoplastic nodules and hepatocellular carcinomas of woodchucks utilizing in situ hybridization and immunocytochemistry.
Hepatocarcinogenesis in woodchucks that are persistently infected with woodchuck hepatitis virus (WHV) follows a progressive course characterized by foci of altered hepatocytes, benign neoplastic nodules and finally hepatocellular carcinoma (HCC). In situ hybridization studies have demonstrated that insulin-like growth factor II (IGF-II) is expressed in most HCCs in woodchucks but that the patterns of expression are variable from tumor to tumor. In some cases, expression of IGF-II is high throughout the tumor, and in others expression is limited to the growing edge of the tumor. IGF-II expression is also activated in focal groups of cells in neoplastic nodules. The major IGF-II mRNA in nodules and HCCs is a 3.4 kb transcript corresponding to one of two IGF-II RNAs in fetal woodchuck liver. A single 15 kDa IGF-II polypeptide accumulates in the perinuclear cytoplasm of hepatocytes in fetal woodchuck liver, neoplastic nodules and HCCs. Thus IGF-II expression in woodchuck liver is reactivated in lesions which are believed to be the precursors of HCC and continues to be expressed as HCCs develop.
Yang
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Marion Bessin Liver Research Center, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
Rogler
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D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000378:metabolism* / Q000382:microbiology; D002455:Cell Division / Q000502:physiology; D005333:Fetus / Q000378:metabolism; D015870:Gene Expression; D006524:Hepatitis, Viral, Animal / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000209:etiology / Q000378:metabolism* / Q000382:microbiology; D008392:Marmota / Q000502:physiology*; D009693:Nucleic Acid Hybridization; D011230:Precancerous Conditions / Q000378:metabolism
D007335:Insulin-Like Growth Factor II