Reactivation of rat insulin-like growth factor II gene during hepatocarcinogenesis

The insulin-like growth factor II (rIGFII) is a mitogenic polypeptide, the expression of which is high in most rat tissues during embryonic development, yet is barely detectable in adult tissues except for some of neurogenic origin. The gene is present as a single copy in the genome but has three alternative leader exons, E1, E2 and E3, thereby with three independent transcriptional promoters. We analysed the expression of rIGFII and the relative efficiency of each promoter in hepatocarcinogen-treated livers, primary hepatomas and established hepatoma lines. The E3-specific product was first detected after 6 weeks of 3'-methyl-4-dimethylaminoazobenzene treatment and those of E1 and E2 also after 9 weeks. The levels gradually increased according to the sum of the treatment period, but reactivation was nil in the regenerating liver. Consistently high levels of expression were observed in all primary tumors, but the relative promoter activity varied with the tumor. The significance of rIGFII reactivation was discussed in the light of the hepatocarcinogenesis.