EXPRESSION OF INSULIN-LIKE-GROWTH-FACTOR-II MESSENGER-RNA IN HEPATOCELLULAR-CARCINOMA

Insulin-like growth factor II (IGF-II) is a mitogenic polypeptide clos ely related to insulin. Its gene has complex regulation of transcripti on, resulting in multiple mRNA initiated by different promoters. To st udy its role in hepatocarcinogenesis, we examined the expression of IG F-II mRNA in hepatocellular carcinomas (HCC) and correlated it with th e pathological features of the rumours. Using northern blot analysis, transcription of the normal adult promoter was repressed in all but tw o of the 30 HCC. Instead, there was re-expression of two foetal transc ripts (6 and 5 kb) in 12 rumours. In contrast, most (93.3%) of the non -tumorous livers showed expression of adult transcript only, and there were three livers demonstrating expression of foetal transcripts in a ddition to the adult one. There was a significant association of IGF-I I expression with direct tumour invasion into the adjacent liver paren chyma but foetal expression did not influence other parameters directl y related to tumour invasiveness, including venous permeation, formati on of tumour microsatellites and positive resection margin. Besides, I GF-II expression was significantly more frequently seen in tumours fro m older patients. To conclude, repression of normal adult promoter and re-expression of foetal promoters of IGF-II are common events in HCC. The observation that foetal IGF-II expression was significantly more frequent in older patients suggests that spontaneous foetal expression of IGF-II late in life may promote the growth of rumours which have a lready arisen through other mechanisms, but foetal reexpression itself is not enough to contribute to tumour progression.