Bcl-2 Gene Family and the Regulation of Programmed Cell Death

Abstract

The genetic control of tumorigenesis has been greatly advanced by the discovery of oncogenes. A central dogma holds that oncogenes induce an overt proliferation providing the driving force for oncogenesis. Cell death has long been recognized as a physiological event during embryonic development. Moreover, a distinct morphological form of cell destruction, apoptosis, had also been described even within cancer tissue (Kerr et al. 1972). In many respects, cancer can be viewed as a violation of normal tissue homeostasis. The maintenance of a relatively constant number of cells in normal tissues reflects a balanced equation between cell proliferation and cell death (Fig. 1). Aberrations of homeostasis that manifest as tumorigenesis would include events that promote proliferation or repress cell death. The history of cancer genetics is replete with examples of oncogenes that promote proliferation. However, bcl-2 provided the first certain example of an oncogene that regulated cell demise. The overexpression of...