DNA Methylation Regulates The Expression Of Trail Receptor Gene And Sensitivity To Apoptosis Induced By Trail In Placental Choriocarcinoma And Transformed Cell Lines

We characterized DNA methylation and gene expression of four TRAIL receptors DR4, DR5, DcRl and DcR2 in three choriocarcinomatic (JAR, JEG-3, BeWo) and two transformed (HTR-8/SVneo and HPT-8) cell lines. DR4 mRNAs were detected in JAR, JEG-3, BeWo and HTR-8/SVneo cells, whereas DR5 was present in all detected cells. DcRl transcripts were expressed in the JAR, JEG-3 and BeWo cells, while DcR2 transcripts were detected only in HTR-8/SVneo and HPT-8. Hypermethylated DR4 promoter was observed in JAR, JEG-3, BeWo and HTR-8/SVneo cells. Hypermethylated DcRl promoter in HTR-8/SVneo and HPT-8 cells, and hypermethylated DcR2 promoter in JAR, JEG-3 and BeWo cells were also detected. Restoration of DR4, DcR1 and DcR2 with decreased DNA methylation of these genes was induced by DNA demethylation agent 5-aza-2’-deoxycytidine (5-aza) in trophoblast cells, while DR5 expression did not exhibit any change. Significant negative correlation between these genes expression and DNA methylation was also observed. In all tested cell lines, only HPT-8 demonstrated sensitivity to TRAIL-induced apoptosis. Combined treatment with 5-aza and TRAIL resulted in apoptosis in JAR, JEG-3, Be Wo and HTR-8/SVneo cells but not in HPT-8 cells. The results indicated DNA methylation was associated with TRAIL receptors expression and might be involved in trophoblast apoptosis.