TUMOR SPECTRUM ANALYSIS IN P53-MUTANT MICE
TUMOR SPECTRUM ANALYSIS IN P53-MUTANT MICE
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DOI：
10.1016/s0960-9822(00)00002-6
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发表时间：
1994-01-01
期刊：
影响因子：
9.2
通讯作者：
WEINBERG, RA
中科院分区：
文献类型：
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作者：
JACKS, T;REMINGTON, L;WEINBERG, RA
背景：p53肿瘤抑制基因在很大比例的人类恶性肿瘤中发生突变，包括结肠癌、乳腺癌、肺癌和脑癌。遗传一个p53突变等位基因的个体易患多种肿瘤类型。该基因编码一种转录调节因子，可能在细胞对DNA损伤的反应中起作用。构建携带p53种系突变的小鼠品系有助于分析p53在正常细胞中的功能和肿瘤发生。结果：为了研究p53突变在体内的影响，我们构建了一株携带该基因种系破坏的小鼠。这种突变消除了大约40%的p53编码能力，并完全消除了p53蛋白的合成。正如先前观察到的不同的p53种系突变，这种p53缺失突变的纯合动物是可以存活的，但高度易患恶性肿瘤。杂合子动物也有更高的癌症风险，尽管这些动物的肿瘤类型分布不同于纯合子突变体。在大多数情况下，杂合动物的肿瘤发生伴随着野生型p53等位基因的缺失。结论：我们重申p53的功能不是正常小鼠发育所必需的，并得出p53状态可以强烈影响肿瘤潜伏期和组织分布的结论。
Background: The p53 tumor suppressor gene is mutated in a large percentage of human malignancies, including tumors of the colon, breast, lung and brain. Individuals who inherit one mutant allele of p53 are susceptible to a wide range of tumor types. The gene encodes a transcriptional regulator that may function in the cellular response to DNA damage. The construction of mouse strains carrying germline mutations of p53 facilitates analysis of the function of p53 in normal cells and tumorigenesis. Results: In order to study the effects of p53 mutation in vivo, we have constructed a mouse strain carrying a germline disruption of the gene. This mutation removes approximately 40 % of the coding capacity of p53 and completely eliminates synthesis of p53 protein. As observed previously for a different germline mutation of p53, animals homozygous for this p53 deletion mutation are viable but highly predisposed to malignancy. Heterozygous animals also have an increased cancer risk, although the distribution of tumor types in these animals differs from that in homozygous mutants. In most cases, tumorigenesis in heterozygous animals is accompanied by loss of the wild-type p53 allele. Conclusion: We reaffirm that p53 function is not required for normal mouse development and conclude that p53 status can strongly influence tumor latency and tissue distribution.