The expression of the death-associated protein kinase (DAPK) protein and promoter methylation in 11 human uterine and ovarian carcinoma cell lines originally established from histopathologically-different carcinoma tissues were examined to investigate the relationship between DAPK and carcinogenesis in female reproductive tissues. The 11 cell lines included three cervical carcinomas, three endometrial carcinomas and five ovarian carcinomas. Western blot analysis showed no detectable expression of DAPK protein in 4 cell lines (ME180, HOKUG, MCAS and OVK-18) while moderate levels of DAPK protein were readily detected in normal human endometrium, and normal murine uterus and ovary. Methylation-specific PCR of the 11 cell lines revealed that 5 carcinoma cell lines (ME180, HOKUG, MCAS, OVK-18 and HEC-1) expressed hypermethylated promoters in the DAPK genes, while DAPK promoters in the other 6 carcinoma cell lines remained unmethylated. These results indicate that DAPK protein expression is reduced or silenced in some human uterine and ovarian carcinoma cells by methylation of the DAPK gene promoter region. Therefore, reduced DAPK expression and methylation of the DAPK promoter may be involved in carcinogenesis of human uterine and ovarian tissues.

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