Mutations in the p53 Tumor Suppressor Gene: Important Milestones at the Various Steps of Tumorigenesis.
Mutations in the p53 Tumor Suppressor Gene: Important Milestones at the Various Steps of Tumorigenesis.
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DOI：
10.1177/1947601911408889
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发表时间：
2011-04-01
期刊：
影响因子：
--
通讯作者：
Rotter, Varda
中科院分区：
文献类型：
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作者：
Rivlin, Noa;Brosh, Ran;Rotter, Varda
p53肿瘤抑制因子的失活是肿瘤发生中的常见事件。在大多数情况下，p53基因发生突变，产生稳定的突变蛋白，其积累被认为是癌细胞的标志。突变的p53蛋白不仅失去了它们的肿瘤抑制活性，而且经常获得额外的致癌功能，赋予细胞生长和存活优势。有趣的是，p53基因的突变被证明发生在恶性转化多步骤过程的不同阶段，因此对肿瘤的启动、促进、侵袭性和转移有不同的贡献。在这里，作者回顾了在肿瘤发生的各个阶段参与p53失活的不同研究，并强调了p53突变在癌症进展的每个阶段的具体贡献。
Inactivation of the p53 tumor suppressor is a frequent event in tumorigenesis. In most cases, the p53 gene is mutated, giving rise to a stable mutant protein whose accumulation is regarded as a hallmark of cancer cells. Mutant p53 proteins not only lose their tumor suppressive activities but often gain additional oncogenic functions that endow cells with growth and survival advantages. Interestingly, mutations in the p53 gene were shown to occur at different phases of the multistep process of malignant transformation, thus contributing differentially to tumor initiation, promotion, aggressiveness, and metastasis. Here, the authors review the different studies on the involvement of p53 inactivation at various stages of tumorigenesis and highlight the specific contribution of p53 mutations at each phase of cancer progression.