DAP-kinase loss of expression in various carcinoma and B-cell lymphoma cell lines : possible implications for role as tumor suppressor gene

• Published in: Oncogene Vol. 15; no. 4; pp. 403 - 407
• Main Authors: KISSIL, J. L, FEINSTEIN, E, COHEN, O, JONES, P. A, TSAI, Y. C, KNOWLES, M. A, EYDMANN, M. E, KIMCHI, A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 24.07.1997; Nature Publishing Group
• Subjects: Ankyrins; Apoptosis; Apoptosis Regulatory Proteins; B-cell lymphoma; Biological and medical sciences; Bladder cancer; Breast cancer; Breast carcinoma; Calcium-binding protein; Calcium-Calmodulin-Dependent Protein Kinases - genetics; Calcium-Calmodulin-Dependent Protein Kinases - physiology; Calmodulin; Cancer; Cell death; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; DAP kinase; Death-Associated Protein Kinases; Demethylation; Fundamental and applied biological sciences. Psychology; Gene expression; Genes, Tumor Suppressor; Humans; Kidney cancer; Kinases; Lymphocytes B; Lymphoma, B-Cell - enzymology; Molecular and cellular biology; mRNA; Neoplasia; Neoplasms - enzymology; Protein-serine/threonine kinase; Renal cell carcinoma; RNA, Messenger - analysis; Tumor cell lines; Tumor Cells, Cultured; Tumor suppressor genes; Tumors; Human; Carcinoma; Enzyme; Transferases; Malignant hemopathy; B-Lymphocyte; Malignant tumor; Gene expression; Lymphoma; Cell line; Protein kinase; Lymphoproliferative syndrome; Methylation; Apoptosis; Tumor suppressor gene
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1201172

DAP-kinase is a novel calmodulin dependent serine/threonine kinase that carries ankyrin repeats and the death domain. It was recently isolated, 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 neoplasms. 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 than 1% compared to the positive cell lines. Interestingly, DAP-kinase expression could be restored in some of the negative bladder carcinoma and B-cell lines by treatment of cells with 5'-azadeoxycytidine that causes DNA demethylation. The high frequency of loss of DAP-kinase expression in human tumor cell lines, and the occasional involvement of methylation in this process raise the possibility that this novel mediator of cell death may function as a tumor suppressor gene.