Expression and LOI of Igf2 in mouse tumors

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Igf2 is expressed in most tissues during a fetal period in mice, while it is suppressed except for the brain in adult. Igf2 is an imprinted gene of which paternal allele is expressed, while its material allele is suppressed. It is suggested that the imprinting of Igf2 is maintained by methylation of the specific regions within the Igf2 gene as well as methylation of the H19 gene which is located downstream of Igf2. The Igf2 gene contains 6 exons, and lgf2 mRNA includes one of exons 1-3 with exons 4-6 in common. On the other hand, since most mouse tumors express Igf2 and since tumors occasionally develop in Igf2 transgenic mice, Igf2 is thought to have a role in tumor development. A purpose of this study was to investigate the allele specific Igf2 expression, methylation of Igf2 gene and transcription start points in mouse tumor cells.Following points became clear in 1998- 1999.(1) By analyzing the polymorphic CA repeat within Igf2 exon 6, loss of imprinting (LOI) was frequently detected in mouse HCC cell lines. On the other hand, LOI was hardly found in liver epithehal (LE) cells derived from the normal liver.(2) All the P1, P2, P3 promoters were active in the HCC cells, while only P2 and P3 promoters were active in LE cells.(3) Igf2 was expressed in the primary cultures of normal hepatocytes, but its imprinting is maintained in this case.(4) Paternal allele specific methylation of CpG was identified by methylation specific PCR-DNA sequencing in the upstream non-coding region in Igf2.