Lowe S W, Bodis S, McClatchey A, Remington L, Ruley H E, Fisher D E, Housman D E, Jacks T
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
Science. 1994 Nov 4;266(5186):807-10. doi: 10.1126/science.7973635.
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.
在免疫功能低下的小鼠中，对表达或缺乏p53肿瘤抑制基因的基因定义肿瘤的治疗反应性进行了比较。表达p53基因的肿瘤含有高比例的凋亡细胞，在用γ射线或阿霉素治疗后通常会消退。相比之下，用相同方案治疗的p53缺陷肿瘤继续增大，且凋亡细胞很少。p53的获得性突变与表达p53的肿瘤的治疗耐药性和复发均相关。这些结果表明，此处由p53失活引起的凋亡缺陷可产生治疗耐药性肿瘤，并提示p53状态可能是肿瘤对治疗反应的重要决定因素。
