title: Insights from Bcl-2 and Myc: malignancy involves abrogation of apoptosis as well as sustained proliferation.
abstract: The chromosome translocations typifying Burkitt's lymphoma and follicular lymphoma deregulate very different oncogenes, myc and bcl-2. Transgenic mouse models have illuminated how each contributes to lymphomagenesis. Constitutive myc expression provokes sustained cell proliferation and retards differentiation. However, the resulting expansion in cell number is self-limiting, because the cells remain dependent on cytokines and undergo apoptosis when these become limiting. In contrast, bcl-2 is the prototype of a new class of oncogene that enhances cell survival but does not promote proliferation. Coexpression of these genes leads to the rapid transformation of lymphocytes, probably because each can counter an antioncogenic aspect of the other. Several close homologues of Bcl-2 also enhance cell survival and are thus potential oncogenes; each is essential for maintenance of particular major organs. More distant Bcl-2 relatives instead promote apoptosis and can be regarded as tumor suppressors. For many but not all apoptic signals, the balance between these competing activities determines cell survival. Learning how to adjust the apoptotic threshold in cancer cells should promote development of more effective therapeutic strategies.
authors: The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria, Australia.
authors: S
authors: S
authors: Cory
authors: D L
authors: DL
authors: Vaux
authors: A
authors: A
authors: Strasser
authors: A W
authors: AW
authors: Harris
authors: J M
authors: JM
authors: Adams
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002051:Burkitt Lymphoma / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D019254:Genes, bcl-2; D016259:Genes, myc; D008224:Lymphoma, Follicular / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D013091:Spermatogenesis / Q000502:physiology