Frequent Biallelic Expression of Insulin-like Growth Factor II (IGF2) in Gynogenetic Ovarian Teratomas: Uncoupling of H19 and IGF2 Imprinting

Human uniparental gestations such as gynogenetic ovarian teratomas provide a model to evaluate the integrity of parent-specific gene expression - i.e. imprinting - in the absence of a complementary parental genetic contribution. The few imprinted genes characterized so far include the insulin-like growth factor-2 gene (IGF2) coding for a fetal growth factor and H19 gene whose normal function is unknown but it is likely to act as an mRNA. IGF2 is expressed by the paternal allele and H19 by the maternal allele. This reciprocal expression is quite interesting because both H19 and IGF2 genes are located close to each other on chromosome 11p15.5. In situ RNA hybridization analysis has shown variable expression of the H19 and IGF2 alleles according to the tissue origin in 11 teratomas. Especially, Skin, derivative of ectoderm, is expressed conspicuously. We examined imprinting of H19 and IGF2 in teratomas using PCR and RT-PCR of exonic polymorphism. H19 and IGF2 transcript could be expressed either biallelically or monoallelically in the teratomas. Biallelic expression (i.e., loss of imprinting) of IGF2 occured in 5 out of 6 mature teratomas and 1 out of 1 immature teratoma. Biallelic expression of H19 occured in 4 out of 10 mature teratomas and 1 out of 1 immature teratoma. Expression levels of H19 and IGF2 transcript using the semi-quantitative RT-PCR had no relation between monoallelic and biallelic expression. Moreover, IGF2 biallelic expression did not affect allele-specificity or levels of H19 expression. These results demonstrate that both genes, H19 and IGF2, can be imprinted, expressed and regulated independently and individually of each other in ovarian teratoma.

Role of IGF2 Gene in Developing Human Ovary / 체질인류학회지

To understand the role of IGF2 gene in development of human ovary, IGF2 expression was detected by monoclonal antibody for IGF2 to its producted protein with immunohistochemical technique on human ovarian tissues. The results was as follows. IGF2 was highly expressed in ovum of mature follicle, IGF2 expression, however, was not high in granulosa and the cells. IGF2 was not highly expressed in ovum of primary follicle. Highly expressed IGF2 was found on corpus luteum and no expression of IGF2 was found in stroma and epithelial cells. These results suggest that IGF2 is important role in ovulation and in production of progesterone. Abnormal IGF2 expression may be concerned to carcinogenesis of ovarian tumor because most of all tumor from ovary is originated from epithelium.