Apoptosis in Burkitt lymphoma cells is driven by c-myc.
Chromosomal translocation and subsequent de-regulation of the c-myc proto-oncogene are considered to be critical events in the multi-stage evolution of Burkitt lymphoma (BL). It is widely accepted that Myc protein functions as a competence factor for proliferation. However, recent studies indicate that it can also act in some cell types as a regulator of apoptosis. BL cell populations display a high frequency of apoptosis in vivo, a property which is also readily demonstrable in vitro in group I BL cell lines. Such lines are known to retain the cell surface marker characteristics of the parental tumour cells and, in the case of Epstein-Barr virus-positive tumours, their restricted viral protein expression. We have shown previously that apoptosis in a group I BL cell line is inhibited by interferon (IFN)-alpha. Here we show that IFN-alpha-mediated suppression of apoptosis in group I BL cells corresponds temporally with inhibition of Myc protein levels. Furthermore, inhibition of Myc expression following treatment with c-myc anti-sense oligonucleotides markedly enhanced survival of group I BL cells. These results indicate that, whilst c-myc may facilitate cycling of tumour cells in which it is de-regulated, it also stimulates their apoptosis.
Milner
A E
AE
Department of Immunology, University of Birmingham Medical School, UK.
Grand
R J
RJ
Waters
C M
CM
Gregory
C D
CD
D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000473:pathology* / Q000503:physiopathology; D002455:Cell Division / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D014407:Tumor Cells, Cultured
D016898:Interferon-alpha; C000715470:MAS1 protein, human; D016376:Oligonucleotides, Antisense; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D015759:Ionomycin