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[Cancer Research 62, 1876-1883, March 15, 2002]
© 2002 American Association for Cancer Research

Tumor Biology

DNA Damage Is Able to Induce Senescence in Tumor Cells in Vitro and in Vivo1

Robert H. te Poele2, Andrei L. Okorokov, Lesley Jardine, Jeffrey Cummings and Simon P. Joel3

Department of Medical Oncology, St. Bartholomew’s Hospital, London EC1A 7BE [R. H. t. P., S. P. J.]; YCR P53 Research Group, Department of Biology, University of York, York YO10 5DD [A. L. O.]; and Imperial Cancer Research Fund, Medical Oncology Unit, Western General Hospital, Edinburgh EH4 2XU [L. J., J. C.], United Kingdom

Often the use of cytotoxic drugs in cancer therapy results in stable disease rather than regression of the tumor, and this is typically seen as a failure of treatment. We now show that DNA damage is able to induce senescence in tumor cells expressing wild-type p53. We also show that cytotoxics are capable of inducing senescence in tumor tissue in vivo. Our results suggest that p53 and p21 play a central role in the onset of senescence, whereas p16INK4a function may be involved in maintaining senescence. Thus, like apoptosis, senescence appears to be a p53-induced cellular response to DNA damage and an important factor in determining treatment outcome.




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