Abstract
Deregulated expression of c-Myc has been shown to induce or enhance apoptosis in various different cell types. c-Myc requires p53 for apoptosis in some but not all the cell types, indicating heterogeneous mechanisms for c-Myc-induced apoptosis. In B lymphoma line WEHI-231, stable expression of c-Myc has been demonstrated to protect cells from BCR-mediated apoptosis. However, stable expression of c-Myc carrying pro-apoptotic functions may generate variant cells resistant to apoptosis. By utilizing an inducible system for c-Myc, we demonstrated here that deregulated expression of c-Myc induced apoptosis of WEHI-231 by itself, indicating that c-Myc induces apoptosis in WEHI-231 as is the case for other cell types. When transactivation of p53 was inactivated, WEHI-231 cells overexpressing c-Myc no longer underwent apoptosis in the absence of other stimuli, but showed markedly enhanced apoptosis in the presence of BCR ligation. These results indicate that deregulated c-Myc expression enhances apoptosis by a p53-independent pathway in the presence of BCR signaling but requires p53 for apoptosis in the absence of BCR crosslinking in WEHI-231. BCR ligation may thus activate a p53-independent pathway of c-Myc-induced apoptosis.
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Acknowledgements
We thank Drs M Bishop, K Seno, S Miyatake, K Maruyama for plasmids. This work was supported in part by grants from the Ministry of Education, Science, Sports and Culture of Japan, the Science and Technology Agency of Japan, the Yamanouchi Foundation for Research on Metabolic Disorders, Ciba-Geigy Foundation (Japan) for the Promotion of Science, and Uehara Memorial Foundation, and the Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Drug ADR Relief, R&D Promotion and Product Review of Japan.
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Hagiyama, H., Adachi, T., Yoshida, T. et al. Signaling through the antigen receptor of B lymphocytes activates a p53-independent pathway of c-Myc-induced apoptosis. Oncogene 18, 4091–4098 (1999). https://doi.org/10.1038/sj.onc.1202772
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DOI: https://doi.org/10.1038/sj.onc.1202772
