Identification of aberrant promoter hypomethylation of HOXA10 in ovarian cancer.

PURPOSE

The purpose of this study was to determine the relationship between hypomethylation of HOXA10 gene's promoter and high expression in malignant ovarian tissues, and to confirm the level of hypomethylation in ovarian cell lines.

EXPERIMENTAL DESIGN

We performed the methylation status of 29 samples from ovarian carcinomas and 16 from normal tissues by methylation-specific polymerase chain reaction (MSP). Then, we evaluated the expression of mRNA and protein of HOXA10 in all samples to work out the relationship between the methylation status of HOXA10 and its expression in transcriptional and translational levels. We then confirmed our present study using SKOV3 and HEY ovarian cancer cell lines treated with the demethylating agent 5-aza-2'-deoxycytidine (5-aza-dC) to detect whether the expression of HoxA10 in the two cell lines was altered.

RESULTS

Increased expression of HOXA10 was detected in almost all ovarian carcinomas (p < 0.05). Promoter hypomethylation was found in (17 of 29) 58.62% ovarian cancers and (4 of 16) 25% normal ovaries (p < 0.05). The HOXA10 expression is higher when the status of HOXA10 gene promoter is hypomethylated than in methylated tissues (p < 0.05). After 5-aza-dC treatment, the expression level of HOXA10 mRNA transcript was increased in the two cell lines.

CONCLUSION

Our results indicate that promoter hypomethylation is an important mechanism for high expression of HOXA10 in human ovarian cancer and may be a potential prognostic factor in ovarian cancer.