Yang D Y, Rogler C E
Marion Bessin Liver Research Center, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
Carcinogenesis. 1991 Oct;12(10):1893-901. doi: 10.1093/carcin/12.10.1893.
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.
持续感染土拨鼠肝炎病毒（WHV）的土拨鼠的肝癌发生遵循一个渐进的过程，其特征为肝细胞改变灶、良性肿瘤结节，最终发展为肝细胞癌（HCC）。原位杂交研究表明，胰岛素样生长因子II（IGF-II）在大多数土拨鼠肝癌中表达，但不同肿瘤之间的表达模式存在差异。在某些情况下，IGF-II在整个肿瘤中高表达，而在其他情况下，表达仅限于肿瘤的生长边缘。IGF-II在肿瘤结节的局部细胞群中也被激活。结节和肝癌中的主要IGF-II mRNA是一种3.4 kb的转录本，对应于胎儿土拨鼠肝脏中两种IGF-II RNA之一。单一的15 kDa IGF-II多肽积聚在胎儿土拨鼠肝脏、肿瘤结节和肝癌的肝细胞的核周细胞质中。因此，土拨鼠肝脏中的IGF-II表达在被认为是肝癌前体的病变中被重新激活，并随着肝癌的发展持续表达。
