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Role of c-myc and p27 in Anti-IgM Induced B-Lymphoma Apoptosis

  • D. W. Scott
  • D. Donjerković
  • B. Maddox
  • S. Ezhevsky
  • T. Grdina
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 224)

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 (Kipl) 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.

Keywords

Growth Arrest Induce Growth Arrest Lymphoma Model Accelerate Cell Death Retinoblastoma Gene Product 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • D. W. Scott
    • 1
  • D. Donjerković
    • 1
  • B. Maddox
    • 1
  • S. Ezhevsky
    • 1
  • T. Grdina
    • 1
  1. 1.Department of Immunology, Holland Laboratory for the Biomedical SciencesAmerican Red CrossRockvilleUSA

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