Role of c-myc and p27 in anti-IgM induced B-lymphoma apoptosis.

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.

• Authors: D W Scott, D Donjerković, B Maddox, S Ezhevsky, T Grdina
• Journal: Current topics in microbiology and immunology (Curr Top Microbiol Immunol) Vol. 224 Pg. 103-12 ( 1997) ISSN: 0070-217X [Print] Germany
• PMID: 9308233 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Antibodies, Anti-Idiotypic
• Cdkn1b protein, mouse
• Cell Cycle Proteins
• Enzyme Inhibitors
• Immunoglobulin M
• Microtubule-Associated Proteins
• Tumor Suppressor Proteins
• Cyclin-Dependent Kinase Inhibitor p27
• Cyclin-Dependent Kinases

Topics

• Animals
• Antibodies, Anti-Idiotypic (pharmacology)
• Apoptosis
• Cell Cycle
• Cell Cycle Proteins
• Cyclin-Dependent Kinase Inhibitor p27
• Cyclin-Dependent Kinases (antagonists & inhibitors)
• Enzyme Inhibitors (metabolism)
• Genes, myc
• Immunoglobulin M (metabolism)
• Lymphoma, B-Cell (genetics, immunology, pathology)
• Mice
• Microtubule-Associated Proteins (metabolism)
• Models, Biological
• Tumor Suppressor Proteins