p53 Status and the Efficacy of Cancer Therapy in Vivo

SW Lowe, S Bodis, A McClatchey, L Remington… - Science, 1994 - science.org
SW Lowe, S Bodis, A McClatchey, L Remington, HE Ruley, DE Fisher, DE Housman…
Science, 1994science.org
The therapeutic responsiveness of genetically defined tumors expressing or devoid of the
p53 tumor suppressor gene was compared in immunocompromised mice. Tumors
expressing the p53 gene contained a high proportion of apoptotic cells and typically
regressed after treatment with gamma radiation or adriamycin. In contrast, p53-deficient
tumors treated with the same regimens continued to enlarge and contained few apoptotic
cells. Acquired mutations in p53 were associated with both treatment resistance and relapse …
The therapeutic responsiveness of genetically defined tumors expressing or devoid of the p53 tumor suppressor gene was compared in immunocompromised mice. Tumors expressing the p53 gene contained a high proportion of apoptotic cells and typically regressed after treatment with gamma radiation or adriamycin. In contrast, p53-deficient tumors treated with the same regimens continued to enlarge and contained few apoptotic cells. Acquired mutations in p53 were associated with both treatment resistance and relapse in p53-expressing tumors. These results establish that defects in apoptosis, here caused by the inactivation of p53, can produce treatment-resistant tumors and suggest that p53 status may be an important determinant of tumor response to therapy.
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