Epigenetic regulation of death-associated protein kinase expression in primary gastric cancers from Chinese patients

Abstract

Death-associated protein kinase (DAPK) is a novel serine/threonine kinase involved in apoptosis and tumor suppression. Promoter methylation is an important mechanism by which tumor suppressor gene transcription is repressed in cancer cells. Although reduced expression and aberrant methylation of DAPK has been reported in various human cancers, including gastric cancer (GC), the results remain discrepant. We aimed to investigate DAPK mRNA and protein expression in primary GC tissues from Chinese patients and establish a possible relationship between the promoter methylation status and the decreased expression of DAPK. The mRNA level, protein expression, and promoter methylation of DAPK were examined, in the cancer tissues and the corresponding, adjacent nontumor tissues of the 62 GC cases, by RT-PCR, western blotting and methylation-specific PCR, respectively. DAPK mRNA and protein expression in GC tissues was significantly reduced compared with corresponding nontumor tissues (P<0.0001). The methylation frequency of the DAPK promoter in primary GC tissues is significantly higher than in the corresponding nontumor tissues (54.8 vs. 17.7%, P<0.0001). Furthermore, DAPK mRNA expression in tissues containing aberrant promoter methylation was significantly reduced compared with GC tissues with unmethylated DAPK promoter (P<0.0001). Moreover, a significant correlation was demonstrated between the TNM stage and the degree of DAPK promoter methylation in primary GCs (P=0.04). DAPK protein and mRNA expression was reduced in GC tissues of Chinese patients. Diminished expression of DAPK was associated with promoter methylation.