The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Bim is a suppressor of Myc-induced mouse B cell leukemia
Open accessAbstract
Impaired apoptosis is now recognized to be central to tumor development. Bcl2, activated by chromosomal translocation in human follicular lymphoma, promotes oncogenesis by inhibiting apoptosis. Bim, a distant proapoptotic relative, is emerging as a major physiologic antagonist of Bcl2. Here, we show that loss of Bim is oncogenic. Bim protein levels were elevated in the apoptosis-prone B lymphoid cells of Eμ- Myc -transgenic mice, and Bim -mutant Eμ- Myc mice had increased numbers of IgM-bearing B cells. Eμ- Myc -expressing B lymphoid cells deficient in Bim were refractory to apoptosis induced in vitro by cytokine deprivation or antigen receptor cross-linking. Thus, Bim is induced by Myc in B cells and mediates apoptosis. Remarkably, inactivation of even a single allele of Bim accelerated Myc-induced development of tumors, particularly acute B cell leukemia. None of the primary tumors from Bim +/- Eμ- Myc mice displayed loss of the second allele of Bim . These findings indicate that Bim is a tumor suppressor, at least in B lymphocytes, and is haploinsufficient. Whereas the p19Arf/p53 pathway is frequently mutated in tumors arising in Bim + / + Eμ- Myc mice, it was unaffected in most Bim-deficient tumors, indicating that Bim reduction is an effective alternative to loss of p53 function.
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Cites
The Bcl2 family: regulators of the cellular life-or-death switch
Cory, S., & Adams, J. M. (2002) · Nature Reviews Cancer · doi:10.1038/nrc883 · Cited by 4,032
Self-citationNoxa, a BH3-Only Member of the Bcl-2 Family and Candidate Mediator of p53-Induced Apoptosis
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p53- and Drug-Induced Apoptotic Responses Mediated by BH3-Only Proteins Puma and Noxa
Villunger, A., Michalak, E. M., Coultas, L., Müllauer, F., Böck, G., Ausserlechner, M. J., Adams, J. M., & Strasser, A. (2003) · Science · doi:10.1126/science.1090072 · Cited by 1,327
Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization
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Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis
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BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes
Bouillet, P., Purton, J. F., Godfrey, D. I., Zhang, L.-C., Coultas, L., Puthalakath, H., Pellegrini, M., Cory, S., Adams, J. M., & Strasser, A. (2002) · Nature · doi:10.1038/415922a · Cited by 782
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Fulda, S., & Debatin, K.-M. (2006) · Oncogene · doi:10.1038/sj.onc.1209608 · Cited by 2,312
Reflecting on 25 years with MYC
Meyer, N., & Penn, L. Z. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2231 · Cited by 1,575
Kuwana, T., Bouchier-Hayes, L., Chipuk, J. E., Bonzon, C., Sullivan, B. A., Green, D. R., & Newmeyer, D. D. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.02.003 · Cited by 1,185
Thirty years of BCL-2: translating cell death discoveries into novel cancer therapies
Delbridge, A. R. D., Grabow, S., Strasser, A., & Vaux, D. L. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2015.17 · Cited by 752
Metadata
- Authors
- Egle, A., Harris, A. W., Bouillet, P., & Cory, S.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-04-12
- Volume
- 101
- Issue
- 16
- Pages
- 6164-6169
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2013194319
- Cited by
- 488
- References
- 7
- FWCI
- 10.50
- Type
- journal article
- Language
- en
- Open access
- bronze
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