title: Prevention of programmed cell death in Burkitt lymphoma cell lines by bcl-2-dependent and -independent mechanisms.
abstract: Burkitt lymphoma (BL) cell lines which retain the phenotypic characteristics of the freshly-isolated tumour cells (group I cells) readily enter programmed cell death (apoptosis) in response to a variety of triggers. By contrast, isogenic BL cells which are phenotypically altered as a result of activation of their resident EBV genome (group-III cells) are highly protected from apoptosis. Phenotypic changes in group-III cells include the up-regulation of the oncogene, bcl-2. Expression of the 26-kDa bcl-2 protein in group-I BL cells following gene transfer was found to afford protection from apoptosis: the degree of protection was proportional to the amount of bcl-2 protein expressed. When group-I bcl-2 transfectants were compared with their group-III counterparts it was found that, whilst bcl-2 made a significant contribution in protecting from entry into apoptosis, hyper-expression of bcl-2 protein in group-I cells (well beyond that of group-III cells) was necessary to attain the high levels of protection observed in group-III cells. These results suggested that additional, bcl-2-independent, survival mechanisms could operate in BL cells. In support of this notion it was also found that: (1) prolonged culture of group-I lines in vitro resulted in enhanced survival in the absence of bcl-2 up-regulation, and (2) exposure of group-I cells to interferon-alpha triggered a bcl-2-independent protective response. The molecular mechanisms of both the bcl-2-dependent and -independent survival pathways remain to be determined.
authors.affiliation: Department of Immunology, Birmingham University Medical School, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Milner
authors.forename: G D
authors.initials: GD
authors.lastname: Johnson
authors.forename: C D
authors.initials: CD
authors.lastname: Gregory
mesh_terms: D017209:Apoptosis; D002051:Burkitt Lymphoma / Q000235:genetics / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D014162:Transfection; D015854:Up-Regulation
chemical_list: D016898:Interferon-alpha; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019204:GTP-Binding Proteins; D002118:Calcium