p53-dependent apoptosis modulates the cytotoxicity of anticancer agents.

Lowe SW, Ruley HE, Jacks T, Housman DE
Cell. 1993 74 (6): 957-67

PMID: 8402885 · DOI:10.1016/0092-8674(93)90719-7

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.

MeSH Terms (18)

Adenovirus E1A Proteins Animals Antineoplastic Agents Apoptosis Cell Cycle Cell Line Cell Line, Transformed Cell Transformation, Neoplastic DNA Embryo, Mammalian Fibroblasts Flow Cytometry Genes, p53 Genes, ras Genotype Mice Oncogenes Transfection

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