P53 STATUS AND THE EFFICACY OF CANCER-THERAPY IN-VIVO
P53 STATUS AND THE EFFICACY OF CANCER-THERAPY IN-VIVO
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DOI：
10.1126/science.7973635
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发表时间：
1994-11-04
期刊：
影响因子：
56.9
通讯作者：
JACKS, T
中科院分区：
文献类型：
--
作者：
LOWE, SW;BODIS, S;JACKS, T
在免疫功能低下小鼠中比较了表达或缺乏p53肿瘤抑制基因的遗传定义肿瘤的治疗反应性。表达p53基因的肿瘤含有高比例的凋亡细胞，并且通常在用γ射线或阿霉素治疗后消退。与此相反，p53基因缺陷的肿瘤用相同的方案治疗继续扩大，并含有很少的凋亡细胞。获得性p53突变与p53表达肿瘤的治疗耐药性和复发相关。这些结果表明，缺陷的细胞凋亡，在这里引起的失活的p53，可以产生治疗耐药的肿瘤，并表明，p53状态可能是一个重要的决定因素，肿瘤治疗反应。
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.