BCL-2: Physiology and role in neoplasia

Deregulation of proto-oncogenes or inhibition of tumor suppressor genes results in the acquisition of a cellular growth advantage, usually manifested as increased proliferation [1]. Many of the mechanisms that mediate these functions have been elucidated, while the function of others still remains to be resolved. Nevertheless, there exists a broad stratification of genes whose alteration is mechanistic in the development of neoplasia. By contrast, bcl-2, which was originally identified in 1984 [2], appears to function by a mechanism independent of the above two categories, and it may be the first described member of a third broad class of genes whose deregulation plays a role in oncogenesis. It appears to act by inhibiting cell death, rather than by stimulating proliferation.