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| P53-DEPENDENT APOPTOSIS SUPPRESSES TUMOR-GROWTH AND PROGRESSION IN-VIVO |
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| Author(s): SYMONDS H, KRALL L, REMINGTON L, SAENZROBLES M, LOWE S, JACKS T, VANDYKE T |
| Source: CELL Volume: 78 Issue: 4 Pages: 703-711 Published: AUG 26 1994 |
| Times Cited: 760 References: 32 |
| Abstract: To determine the contribution of p53 loss to tumor progression, we have induced abnormal proliferation in the brain choroid plexus epithelium of transgenic mice using a SV40 T antigen fragment that perturbs pRB family function but does not affect p53 function. Tumors induced by this mutant develop slowly compared with those induced by wild-type T antigen. Suppressed tumor growth is directly attributable to p53 function, since rapid tumor development occurs when the T antigen fragment is expressed in p53-null mice. In p53-heterozygous mice, stochastic loss of the wildtype p53 allele results in the focal emergence of aggressive tumor nodules characteristic of tumor progression. In each case, aggressive tumor development in the absence of p53 function corresponds to a decrease in the level of apoptosis. These results provide in vivo evidence that p53-dependent apoptosis, occurring in response to oncogenic events, is a critical regulator of tumorigenesis. |
| Document Type: Article |
| Language: English |
| Reprint Address: SYMONDS, H (reprint author), UNIV N CAROLINA, DEPT BIOCHEM & BIOPHYS, CHAPEL HILL, NC 27599 USA |
Addresses:
1. MIT, CTR CANC RES, CAMBRIDGE, MA 02139 USA
2. UNIV PITTSBURGH, SCH MED, DEPT PEDIAT, PITTSBURGH, PA 15213 USA |
| Publisher: CELL PRESS, 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: PD693 |
| ISSN: 0092-8674 |
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