Promoter methylation of death-associated protein kinase and its role in irradiation response in cervical cancer

Abstract

This study was aimed at investigating the death-associated protein kinase (DAPK) promoter methylation and its clinical relevance in cervical cancer. The DAPK promoter methylation was detected by methylation-specific PCR (MSP) and correlated with DAPK mRNA and protein expression. The effect of DAPK expression on the radiosensitivity of the cervical cancer cell line was assessed by overexpressing DAPK in the radioresistant cell line SiHa. DAPK hypermethylation was found in 56.08% of the cervical cancer samples and was associated with the tumor histological cell type of squamous cell carcinoma (p=0.002) and advanced tumor stage (p=0.005). Subsequently, DAPK protein expression was found to significantly decrease in cervical cancer samples when compared to normal tissues. The DAPK mRNA and protein expression levels were absent or remarkably reduced in SiHa and HeLa in which the DAPK promoter was hypermethylated. The expression levels of DAPK could be restored after demethylation treatment with 5-aza-2′-deoxycytidine. Overexpressing DAPK in vitro had no significant influence to the survival of the radioresistant SiHa cell after being challenged by irradiation. Our findings suggest that DAPK might not directly be responsible for the cellular radio-sensitivity, however, DAPK hypermethylation appeared to be of prognostic significance in the advanced stages of cervical cancer.