| | |  | | | | Record from Web of Science® | | | | | | |
| Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis |
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| Author(s): Wahl AF, Donaldson KL, Fairchild C, Lee FYF, Foster SA, Demers GW, Galloway DA |
| Source: NATURE MEDICINE Volume: 2 Issue: 1 Pages: 72-79 Published: JAN 1996 |
| Times Cited: 509 References: 44 |
| Abstract: The anticancer agent paclitaxel (Taxol(R)) stabilizes tubulin polymerization resulting in arrest in mitosis and apoptotic cell death. Normal human fibroblasts depleted of functional p53 by SV40 T antigen or HPV-16 E6, and primary embryo fibroblasts from p53 null mice showed seven- to ninefold increased cytotoxicity by paclitaxel. Reduced levels of p53 correlated with increased G2/M phase arrest, micronucleation, and p53-independent paclitaxel-induced apoptosis. Surviving cells with intact p53 progressed through mitosis and transiently accumulated in the subsequent G1 phase, coincident with increased p53 and p21(cip1,waf1) protein levels. These results are in contrast to studies linking p53 loss with resistance to DNA damaging anticancer agents. |
| Document Type: Article |
| Language: English |
| Reprint Address: Wahl, AF (reprint author), BRISTOL MYERS SQUIBB PHARMACEUT RES INST, 3005 1ST AVE, SEATTLE, WA 98121 USA |
Addresses:
1. BRISTOL MYERS SQUIBB PHARMACEUT RES INST, PRINCETON, NJ 08543 USA
2. FRED HUTCHINSON CANC RES CTR, CANC BIOL PROGRAM, SEATTLE, WA 98104 USA |
| Publisher: NATURE PUBLISHING CO, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental |
| IDS Number: TP579 |
| ISSN: 1078-8956 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |