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| MYC-MEDIATED APOPTOSIS IS BLOCKED BY ECTOPIC EXPRESSION OF BCL-2 |
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| Author(s): WAGNER AJ, SMALL MB, HAY N |
| Source: MOLECULAR AND CELLULAR BIOLOGY Volume: 13 Issue: 4 Pages: 2432-2440 Published: APR 1993 |
| Times Cited: 215 References: 61 |
| Abstract: 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 la 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 la 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV CHICAGO, BEN MAY INST, CHICAGO, IL 60637 USA
2. UNIV CHICAGO, DEPT BIOCHEM & MOLEC BIOL, CHICAGO, IL 60637 USA
3. UNIV CHICAGO, DEPT PHARMACOL & PHYSIOL SCI, CHICAGO, IL 60637 USA
4. UNIV MED & DENT NEW JERSEY, NEW JERSEY MED SCH, DEPT MICROBIOL & MOLEC GENET, NEWARK, NJ 07103 USA |
| Publisher: AMER SOC MICROBIOLOGY, 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: KT913 |
| ISSN: 0270-7306 |
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