Chapter title |
Role of c-myc and p27 in anti-IgM induced B-lymphoma apoptosis.
|
---|---|
Chapter number | 10 |
Book title |
C-Myc in B-Cell Neoplasia
|
Published in |
Current topics in microbiology and immunology, January 1997
|
DOI | 10.1007/978-3-642-60801-8_10 |
Pubmed ID | |
Book ISBNs |
978-3-64-264560-0, 978-3-64-260801-8
|
Authors |
Scott, D W, Donjerković, D, Maddox, B, Ezhevsky, S, Grdina, T, Scott, D. W., Donjerković, D., Maddox, B., Ezhevsky, S., Grdina, T. |
Abstract |
Crosslinking membrane IgM receptors on a set of murine B cell lymphomas leads to a rapid increase in c-myc, followed by a decrease in its expression to undetectable levels by 8-24 hours. These cells die soon thereafter via apoptosis. IgD receptor crosslinking also leads to an increase in c-myc expression, but it remains above baseline levels for more than 24 hours; these cells continue to proliferate and do not die. We previously reported that antisense oligonucleotides for c-myc prevented growth arrest and cell death in these lymphomas, independent of the presence of mitogenic CpG motifs. Indeed, antisense for c-myc actually led to a stabilization of c-myc message and protein. Growth arrest in these cells is dependent on the increased synthesis of the p27 cyclin kinase inhibitor (Kip1) normally induced after anti-IgM crosslinking. Consistent with its biologic effects, anti-IgD does not cause an increase in p27. Since dexamethasone causes a loss of myc and synergizes with the anti-IgM signal, we suggest that accelerated cell death with this steroid in the presence of anti-IgM is due to a more rapid degradation of this oncogene product. Finally, we propose that c-myc drives the transcription or activation of an inhibitor of the p27 Kip (Kipi). Hence, loss of c-myc in response to anti-IgM signals in these B-cell lymphomas leads to upregulation of p27, growth arrest and apoptosis. It follows that maintenance of c-myc in these B-cell lymphomas should lead to survival and no increase in p27. |
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Other | 1 | 14% |
Student > Master | 1 | 14% |
Researcher | 1 | 14% |
Other | 0 | 0% |
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Medicine and Dentistry | 1 | 14% |
Other | 0 | 0% |