DNA damage is able to induce senescence in tumor cells in vitro and in vivo.
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 p16(INK4a) 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.
te Poele
Robert H
RH
Department of Medical Oncology, St. Bartholomew's Hospital, London.
Okorokov
Andrei L
AL
Jardine
Lesley
L
Cummings
Jeffrey
J
Joel
Simon P
SP
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D004249:DNA Damage / Q000502:physiology*; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D000077146:Irinotecan; D020360:Neoadjuvant Therapy; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000502:physiology; D001616:beta-Galactosidase / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D000077146:Irinotecan; D001616:beta-Galactosidase; D002166:Camptothecin