PROGRAMMED CELL-DEATH BY BCL-2-DEPENDENT AND INDEPENDENT MECHANISMS IN B-LYMPHOMA CELLS

被引:156
作者
CUENDE, E [1 ]
ALESMARTINEZ, JE [1 ]
DING, LY [1 ]
GONZALEZGARCIA, M [1 ]
MARTINEZA, C [1 ]
NUNEZ, G [1 ]
机构
[1] UNIV MICHIGAN, SCH MED, DEPT PATHOL, ANN ARBOR, MI 48109 USA
关键词
APOPTOSIS; BCL-2; B-LYMPHOMA CELLS; PROGRAMMED CELL DEATH; PROTOONCOGENE;
D O I
10.1002/j.1460-2075.1993.tb05799.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Programmed cell death (PCD) or apoptosis is a common form of cellular demise during embryogenesis, tumorigenesis and clonal selection in the immune system. The bcl-2 proto-oncogene has been recently implicated as a potential physiological regulator of the PCD pathway. Gene transfer studies have shown that overexpression of bcl-2 blocks apoptosis mediated by several stimuli in cultured cell lines and promotes the survival of B and T lymphocytes in transgenic mice. However, it remains unclear whether under normal conditions bcl-2 is responsible for controlling cell death. We have investigated the role of bcl-2 in the anti-membrane IgM (mIgM-induced apoptotic death of WEHI-231 B cell lymphoma, a model that mimics clonal deletion of immature B cells by antigen. Signalling of mIgM receptors triggered downregulation of both bcl-2 RNA and protein, and induced apoptosis in WEHI-231 B cells. This effect appeared to be specific since (i) the levels of beta2-microglobulin and beta-actin RNA remain unchanged and (ii) signalling of the apoptosis-resistant B cell lymphoma line BAL-17 with anti-mu was not associated with downregulation of bcl-2 RNA. However, stable expression of bcl-2 by transfection did not rescue WEHI-231 B cells from apoptosis, yet WEHI-231 cells overexpressing bcl-2 were more resistant to programmed cell death induced by heat-shock. These results suggest that depending on the cell lineage, both bcl-2-sensitive and -resistant mechanisms of cell death leading to apoptosis are present and we conclude therefore that in addition to bcl-2, other proteins are important in the apoptosis of WEHI-231 B lymphoma cells.
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收藏
页码:1555 / 1560
页数:6
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