© 1991 Oxford University Press
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Analysis of insulin-like growth factor II (IGF-II) expression in neoplastic nodules and hepatocellular carcinomas of woodchucks utilizing in situ hybridization and imununocytochemistry
Marion Bessin Liver Research Center, Department of Medicine, Albert Einstein College of Medicine 1300 Morris Park Avenue, Bronx, NY 10461, USA
1To whom correspondence should be addressed
Hepatocarcinogenesis in woodchucks that are persistently infected with woodchuck hepatitis virus (WHY) 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.
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