DAP-KINASE LOSS OF EXPRESSION IN VARIOUS CARCINOMA AND B-CELL LYMPHOMA CELL-LINES - POSSIBLE IMPLICATIONS FOR ROLE AS TUMOR-SUPPRESSOR GENE

DAP-kinase is a novel calmodulin dependent serine/threonine kinase tha t carries ankyrin repeats and the death domain. It was recently isolat ed, by a functional selection approach of gene cloning, as a positive mediator of programmed cell death. In this study the expression of DAP -kinase was examined in the cell lines derived from various human neop lasms, DAP-kinase mRNA and protein expression were below the limit of detection in eight out of ten neoplastic derived B-cell lines. In six out of 14 examined bladder carcinoma, in three out of five renal cell carcinoma, and in four out of ten tested breast carcinoma cell lines, the DAP-kinase protein levels were below detection limits or lower tha n 1% compared to the positive cell lines. Interestingly, DAP-kinase ex pression could be restored in some of the negative bladder carcinoma a nd B-cell lines by treatment of cells with 5'-azadeoxycytidine that ca uses DNA demethylation. The high frequency of loss of DAP-kinase expre ssion in human tumor cell lines, and the occasional involvement of met hylation in this process raise the possibility that this novel mediato r of cell death may function as a tumor suppressor gene.