Two-dimensional database of a Burkitt lymphoma cell line (DG 75) proteins:Protein pattern changes following treatment with 5 '-azycytidine

Hypermethylation is an important mechanism for repression of tumor gene sup pressor in cancer. The drug 5'-azacytidine (AZC) has been used as demethyla ting agent to induce the expression of previously silencing genes. In the p resent work, we attempted to determine, using proteomics, the changes in pr otein expression profiles following a treatment of an Epstein Barr virus (E BV)-negative Burkitt lymphoma (BL) cell line DG 75. The effects of the trea tment in terms of cell viability and growth were first examined. The follow ing observations were made: AZC treatment led to (i) a decrease in cell gro wth with an arrest of the cell at G0/G1 phase of the cell cycle, (ii) the e xpression of p16, a tumor-suppressor gene whose expression was dependent on its promoter demethylation. Proteomic study evidenced that AZC treatment a ffected protein expression in two different ways. Twenty-one polypeptides w ere down-expressed, while 14 showed an increased expression. Some of the up regulated proteins appeared related to the energy metabolism, to organizati on of cytoskeletal structures, and to cell viability and protein synthesis. We also established a reference map for proteins in DG 75 cell line, compr ising 74 different polypeptides corresponding to 67 proteins. This map will be accessible via Internet as a resource for proteome analyses of B-cells. Taken together the results presented here highlight new insights into lymp homa cell gene regulations following a treatment of lymphoma cells with AZC and illustrate a use of proteomics to evidence the direct and indirect eff ects of a drug and the pathways it possibly regulates.