Allelic imbalance of insulin-like growth factor II gene expression in cancerous and precancerous lesions of the liver

Abstract

Allelic imbalance of the insulin-like growth factor II (IGF II) gene expression is often seen in hepatocellular carcinoma (HCC).Insulin-like growth factor II (IGF II) is a single-chain polypeptide that exerts its growth-stimulative effect through the IGF I receptor. The IGF II is speculated to serve as an autocrine growth factor in various cancers, because they often coexpress the IGF II and the IGF I receptor. [1][2][3][4] The IGF II gene expression is monoallelic in all the normal tissues other than the liver because of the imprinting of the maternal allele. However, interestingly, most of the cancers arising in these tissues, such as lung cancers, breast cancers, esophageal cancers, Wilms' tumor, and cervical cancers, are reported to show biallelic expression (relaxation) of the IGF II gene. [5][6][7][8][9][10]

Molecular Changes in Hepatocellular Dysplastic Nodules on Microdissected Liver Biopsies

“…Yamada et al 23 found the same insulinlike growth factor receptor II gene allelic loss in both dysplastic nodules and the adjacent cirrhotic tissue. The allelic imbalance of insulin-like growth factor II was also demonstrated by Aihara et al 24 in 3 of 7 dysplastic nodules.…”

Identification of differentially expressed genes in hepatocellular carcinoma with cDNA microarrays

“…Concerning insulin-like growth factor II, there have been reports that it was positive in 60% of HBsAg-positive HCCs, 25.6% of HBsAg-negative HCCs, and some benign neoplastic lesions, 38 and that its expression was enhanced in dysplastic nodules, but not in well-differentiated or moderately differentiated HCCs. 39 According to our results, the mean expression rate of insulin-like growth factor II was 0.76, and it was enhanced 2-fold or more in 1 patient, but reduced to 0.5 or less in 3 patients. Its expression rates in Cases 2 and 3, in whom HBsAg was positive, were 0.90 and 0.60, respectively, indicating no clear enhancement.…”

Focal overexpression of insulin-like growth factor 2 by hepatocytes and cholangiocytes in viral liver cirrhosis

“…IGF-2 gene expression is controlled by mechanisms such as parental imprinting resulting in downregulation of one allele. In HCC, loss of heterozygosity and changes in the methylation patterns within the IGF-2 genes have been documented, and the perturbation of these control mechanisms seems to result in upregulation of IGF-2 expression from promoters characteristic of foetal development (Aihara et al, 1998). Moreover, differential usage of foetal and adult IGF-2 promoters was observed in premalignant proliferations present in HCV-related chronic liver disease (Tanaka et al, 1996).…”

“…In HCC, large proportions of the IGF-2-mRNA were found as splice forms characteristic for foetal tissues (Cariani et al, 1988). An allelic imbalance of IGF-2 gene expression correlating with the loss of maternal imprinting patterns was also considered to have a role in hepatocarcinogenesis (Aihara et al, 1998;Schwienbacher et al, 2000).…”