PMID: 8950469Oct 1, 1996Paper

Lessons from bcl-2 transgenic mice for immunology, cancer biology and cell death research

Behring Institute Mitteilungen
A StrasserA W Harris

Abstract

The protein product of the proto-oncogene bcl-2, originally discovered by virtue of its chromosomal translocation in human follicular centre B cell lymphoma, is a physiological inhibitor of programmed cell death, apoptosis. Initial studies in transgenic mice overexpressing Bcl-2 in B or T lymphocytes demonstrated that Bcl-2 can potently antagonise cell death induced by multiple independent signal transduction routes and can contribute to oncogenesis, particularly in combination with other oncogenes, like c-myc, that promote cell proliferation. Further investigations using crosses between bcl-2 transgenic mice and T cell receptor or immunoglobulin transgenic mice or mutant mice deficient in proper antigen receptor gene rearrangement demonstrated that Bcl-2 can only block death of cells that failed to receive a positive stimulus, "death by neglect', but not activation induced apoptosis. Collectively, these results provide evidence that distinct signalling pathways for apoptosis converge upon a common effector machinery where Bcl-2 acts as an antagonist, but that there also exists a mechanism that can either bypass the Bcl-2 checkpoint or override its protective function. These experimental data are reviewed here and discussed in ...Continue Reading

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