Expression of insulin-like growth factor II mRNA in hepatocellular carcinoma

Abstract

Insulin-like growth factor II (IGF-II) is a mitogenic polypeptide closely related to insulin. Its gene has complex regulation of transcription, resulting in multiple mRNA initiated by different promoters. To study its role in hepatocarcinogenesis, we examined the expression of IGF-II mRNA in hepatocellular carcinomas (HCC) and correlated it with the pathological features of the tumours. Using northern blot analysis, transcription of the normal adult promoter was repressed in all but two of the 30 HCC. Instead, there was re-expression of two foetal transcripts (6 and 5 kb) in 12 tumours. 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 addition to the adult one. There was a significant association of IGF-II expression with direct tumour invasion into the adjacent liver parenchyma but foetal expression did not influence other parameters directly related to tumour invasiveness, including venous permeation, formation of tumour microsatellites and positive resection margin. Besides, IGF-II expression was significantly more frequently seen in tumours from 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 tumours which have already arisen through other mechanisms, but foetal re-expression itself is not enough to contribute to tumour progression.