Alterations in Promoter Usage and Expression Levels of Insulin-like Growth Factor-II and H19 Genes in Ovarian Cancers

Kim, Yun Ah; Lee, Chan; Kim, Seung Jo; Lee, Sun Young; Kim, In Ho; Na, Young Jeong; Jeong, Sang Geun

Abstract

OBJECTIVE
To establish the possible role of imprinting in ovarian cancer, we determined the imprinting status of both IGF-2 and H-19 genes in ovarian cacner, borderline tumors of ovary, benign ovarian tumor and normal ovarian tissues.
METHODS
An allelictyping assay was performed using a PCR-RFLP-based method for identification of heterozygous informative cases. The usage of Insulin-like growth factor-II (IGF-2) promoters was examined by RT-PCR using promoter-specific primers. The mRNA expression of IGF-2 and H19 was quantified using a densitometer.
RESULTS
Loss of imprinting (LOI) of IGF-2 was observed in the order of borderline tumor (77%)>cancer (71%)>benign tumor (60%)>normal ovarian tissues (50%) respectively. And the LOI of H19 gene was not detected in the normal and benign tissues but observed in the borderline tumor and cancer tissues, respectively. The usage of promoter P1, P2, P3 and P4 were observed different pattern in normal, benign tumor, borderline tumor and cancer tissues. The activity of mRNA expression of promoter P4 was higher than other promoters. The cancer tissues predominantly used promoter P1, P2 with relative silencing of the promoter P3. The ovarian cancer tissues showed the higher expression levels of the IGF-2 but a down- regulation of the H19 relative to normal tissues.
CONCLUSION
These results suggest that LOI, deregulation of the IGF-2 promoters, and the altered expression levels of the IGF-2 and H19 gene might be associated with progression of ovarian cancer.