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| P53-DEPENDENT APOPTOSIS MODULATES THE CYTOTOXICITY OF ANTICANCER AGENTS |
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| Author(s): LOWE SW, RULEY HE, JACKS T, HOUSMAN DE |
| Source: CELL Volume: 74 Issue: 6 Pages: 957-967 Published: SEP 24 1993 |
| Times Cited: 2,502 References: 61 |
| Abstract: Although the primary cellular targets of many anticancer agents have been identified, less is known about the processes leading to the selective cell death of cancer cells or the molecular basis of drug resistance. p53-deficient mouse embryonic fibroblasts were used to examine systematically the requirement for p53 in cellular sensitivity and resistance to a diverse group of anticancer agents. These results demonstrate that an oncogene, specifically the adenovirus E1A gene, can sensitize fibroblasts to apoptosis induced by ionizing radiation, 5-fluorouracil, etoposide, and adriamycin. Furthermore, the p53 tumor suppressor is required for efficient execution of the death program. These data reinforce the notion that the cytotoxic action of many anticancer agents involves processes subsequent to the interaction between drug and cellular target and indicate that divergent stimuli can activate a common cell death program. Consequently, the involvement of p53 in the apoptotic response suggests a mechanism whereby tumor cells can acquire cross-resistance to anticancer agents. |
| Document Type: Article |
| Language: English |
| Reprint Address: LOWE, SW (reprint author), MIT, CTR CANC RES, CAMBRIDGE, MA 02139 USA |
Addresses:
1. MIT, DEPT BIOL, CAMBRIDGE, MA 02139 USA
2. VANDERBILT UNIV, MED CTR, SCH MED, DEPT MICROBIOL & IMMUNOL, NASHVILLE, TN 37232 USA |
| Publisher: CELL PRESS, 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: LY493 |
| ISSN: 0092-8674 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |