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Prevention of programmed cell death in burkitt lymphoma cell lines by bcl ‐2‐dependent and ‐independent mechanisms
Author(s) -
Milner Anne E.,
Johnson Gerald D.,
Gregory Christopher D.
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910520424
Subject(s) - apoptosis , biology , programmed cell death , cell culture , lymphoma , in vitro , phenotype , transfection , microbiology and biotechnology , cell , gene , cancer research , immunology , genetics
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‐1 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‐1 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‐1 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: (I) prolonged culture of group‐1 lines in vitro resulted in enhanced survival in the absence of bcl ‐2 up‐regulation, and (2) exposure of group‐1 cells to interferon‐α triggered a bcl ‐2‐independent protective response. The molecular mechanisms of both the bcl ‐2‐dependent and ‐independent survival pathways remain to be determined. © 1992 Wiley‐Liss, Inc.