Gene expression during camptothecin-induced apoptosis in human myeloid leukemia cell line ML-2.

Malignant cell proliferation and accumulation depends on the balance between the rates of cell production and cell death. Recent evidence indicates that apoptosis is important in the development of cancer. Apoptosis is strictly controlled by various regulators, which can take part in the apoptotic process, proliferation and differentiation alike. Apoptosis was induced in myeloid cell line ML-2 by camptothecin, an inhibitor of topoisomerase I. After 18 hours of induction by camptothecin 50% of cells were apoptotic. The apoptotic effect of CAM was reversible in the cells studied. The induction of apoptosis influenced the expression of apoptosis and cell cycle regulators as detected by cDNA arrays, RT-PCR or Western blotting. According to cDNA arrays e.g. bax, bfl1, bak, pRb2, c-jun, jun-B were upregulated, and cdk4, cyclin B1, wee1, CRAF1, DP1 were downregulated. A number of other regulators like p21 and cdc25A, as well as some other genes linked with apoptosis, as p53 and the bcl-2 family, were up- or down-regulated as determined by real-time PCR. Changes in gene expression were found not only in the group of regulators of apoptosis and the cell cycle, but also among regulators of differentiation.