PREVENTION OF PROGRAMMED CELL-DEATH IN BURKITT-LYMPHOMA CELL-LINES BY BCL-2-DEPENDENT AND BCL-2-INDEPENDENT MECHANISMS

被引:80
作者
MILNER, AE [1 ]
JOHNSON, GD [1 ]
GREGORY, CD [1 ]
机构
[1] UNIV BIRMINGHAM,SCH MED,DEPT IMMUNOL,VINCENT DR,BIRMINGHAM B15 2TT,W MIDLANDS,ENGLAND
关键词
D O I
10.1002/ijc.2910520424
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页码:636 / 644
页数:9
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