anisomycin and Leukemia--Erythroblastic--Acute

The proto-oncogene c-Jun has been implicated in the control of cell proliferation and differentiation and more recently in the regulation of apoptosis. We have previously reported the involvement of c-Jun in the erythroid differentiation block in murine erythroleukemia (MEL) cells. As reported here, we investigated the role of c-Jun in the regulation of terminal differentiation and apoptosis of MEL cells by studying different stable transfectant clones containing c-jun constructs in sense or antisense orientation. c-Jun did not prevent cell growth arrest in G0/G1 and p21 induction that are normally associated with terminal differentiation induced by DMSO treatment, suggesting that c-Jun may uncouple phenotypic differentiation and terminal cell division in the MEL cell system. Spontaneous apoptosis was accelerated in c-jun expressing MEL cells before and after DMSO treatment. Moreover, c-Jun sensitized apoptosis induced by various drugs. Drug-induced apoptosis was associated with c-Jun N-terminal kinase (JNK) activation and c-Jun N-terminal phosphorylation (JNP). In contrast, overexpression of c-jun delayed apoptosis in serum-starved cells, indicating that c-Jun may reduce or accelerate apoptosis in MEL cells depending on the nature of the apoptotic stimulus. These results suggest that the proto-oncogene c-Jun may modulate differentiation and apoptosis of leukemic cells.

Topics: Animals; Anisomycin; Antibiotics, Antineoplastic; Apoptosis; Cell Differentiation; Culture Media, Serum-Free; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Daunorubicin; Dimethyl Sulfoxide; DNA, Antisense; Enzyme Activation; Enzyme Inhibitors; Etoposide; Gene Expression Regulation, Leukemic; Genes, jun; JNK Mitogen-Activated Protein Kinases; Leukemia, Erythroblastic, Acute; Mice; Mitogen-Activated Protein Kinases; Neoplasm Proteins; Phosphorylation; Protein Processing, Post-Translational; Protein Synthesis Inhibitors; Proto-Oncogene Proteins c-jun; Recombinant Fusion Proteins; Topoisomerase II Inhibitors; Transfection; Tumor Cells, Cultured