Myc-mediated apoptosis is blocked by ectopic expression of Bcl-2.
The product of the c-myc proto-oncogene is an important positive regulator of cell growth and proliferation. Recently, c-Myc has also been demonstrated to be a potent inducer of apoptosis when expressed in the absence of serum or growth factors. To further examine Myc-induced apoptosis, we coexpressed the proto-oncogene bcl2, which has been shown to block apoptosis in other systems, with c-myc in serum-deprived Rat 1a fibroblasts. Here we report that ectopic expression of bcl2 specifically blocks apoptosis induced by constitutive c-myc expression. Constitutive c-myc expression in serum-deprived Rat 1a cells caused a > 15-fold increase in the number of dead cells, accompanied by DNA fragmentation. However, coexpression of bcl2 with c-myc in these cells led to a 10-fold increase in the number of live cells and a significant decrease in DNA fragmentation. Thus, Bcl-2 effectively inhibits Myc-induced apoptosis in serum-deprived Rat 1a fibroblasts without blocking entry into the cell cycle. These results imply that apoptosis serves as a protective mechanism to prevent tumorigenicity elicited by deregulated Myc expression. This protective mechanism is abrogated, however, by Bcl-2 and therefore may explain the synergism between Myc and Bcl-2 observed in certain tumor cells.
Wagner
A J
AJ
Ben May Institute, Department of Biochemistry and Molecular Biology, University of Chicago, Illinois 60637.
Small
M B
MB
Hay
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D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002478:Cells, Cultured; D003470:Culture Media; D004249:DNA Damage; D015870:Gene Expression; D016259:Genes, myc; D005822:Genetic Vectors; D066298:In Vitro Techniques; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012190:Retroviridae; D014162:Transfection
D003470:Culture Media; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger