Unger C, Buchmann A, Bünemann C L, Kress S, Schwarz M
Institute of Toxicology, University of Tübingen, Wilhelmstr. 56, 72074 Tübingen, Germany.
Cell Death Differ. 1998 Jan;5(1):87-95. doi: 10.1038/sj.cdd.4400321.
The role of the tumor suppressor protein p53 in apoptosis of mouse hepatoma cells was studied. Different lines were used which were either p53 wild-type or carried various types of heterozygous or homozygous p53 mutations. The presence of mutations was demonstrated to correlate with a lack in transactivating activity of p53. While UV-light effectively produced apoptosis in cells of all lines, irrespective of their p53 mutational status, gamma-irradiation induced the formation of micronuclei but failed to induce apoptosis. Both UV- and gamma-irradiation led to nuclear accumulation and increases in p53 protein in p53 wild-type cells. Similarly, no significant differences in apoptotic response between p53 wild-type and p53 mutated cells were seen with other apoptotic stimuli like CD95/APO-1/Fas or TNFalpha. These data suggest that wild-type p53 is not required for induction of apoptosis in mouse hepatoma cells which may explain the apparent lack of p53 mutations in mouse liver tumors.
研究了肿瘤抑制蛋白p53在小鼠肝癌细胞凋亡中的作用。使用了不同的细胞系，这些细胞系要么是p53野生型，要么携带各种类型的杂合或纯合p53突变。已证明突变的存在与p53的反式激活活性缺乏相关。虽然紫外线能有效诱导所有细胞系的细胞凋亡，无论其p53突变状态如何，但γ射线诱导了微核的形成，但未能诱导凋亡。紫外线和γ射线均导致p53野生型细胞中p53蛋白的核积累和增加。同样，在其他凋亡刺激如CD95/APO-1/Fas或TNFα作用下，p53野生型细胞和p53突变细胞之间的凋亡反应没有显著差异。这些数据表明，野生型p53不是诱导小鼠肝癌细胞凋亡所必需的，这可能解释了小鼠肝肿瘤中明显缺乏p53突变的现象。
