Expression of insulin-like growth factor I (IGF-I) and IGF-II mRNA during hepatic development, proliferation and carcinogenesis in the rat.

Insulin-like growth factor I (IGF-I) and IGF-II are peptides that presumably are required for normal fetal and postpubertal growth. The production of IGFs is developmentally regulated and the liver appears to be a major site of production. By analysing mRNA levels for IGF-I and IGF-II in the rat liver we have attempted to further study the expression of these growth factors during development and regeneration as well as during the course of hepatic carcinogenesis. Fetal livers are characterized by a high level of IGF-II mRNA and a low level of IGF-I mRNA, while in adult livers the opposite situations occur, i.e. a high level of IGF-I mRNA and a non-measurable level of IGF-II mRNA. During the course of experimentally induced hepatic cancer, IGF-I mRNA was consistently reduced and in a majority of cancers analysed (6/9) IGF-II mRNA was increased, i.e. a fetal type of IGF expression can be switched on in some experimentally induced hepatocellular carcinomas. The onset of IGF-II production during hepatic carcinogenesis appears to be a late phenomenon since liver nodules, preceding the development of hepatocellular cancer, were found not to contain IGF-II mRNA. Furthermore, during hepatic regeneration following partial hepatectomy no marked change in IGF-I or IGF-II mRNA levels was noted. The above results suggest that the fetal growth factor IGF-II could have a role in hepatic cancer.