p53活性持续升高的小鼠中的肿瘤抑制与正常衰老
Tumor suppression and normal aging in mice with constitutively high p53 activity.
作者信息
Mendrysa Susan M, O'Leary Kathleen A, McElwee Matthew K, Michalowski Jennifer, Eisenman Robert N, Powell Douglas A, Perry Mary Ellen
机构信息
Department of Oncology, University of Wisconsin, Madison, 53706, USA.
出版信息
Genes Dev. 2006 Jan 1;20(1):16-21. doi: 10.1101/gad.1378506.
Abstract
The p53 inhibitor murine double-minute gene 2 (Mdm2) is a target for potential cancer therapies, however increased p53 function can be lethal. To directly address whether reduced Mdm2 function can inhibit tumorigenesis without causing detrimental side effects, we exploited a hypomorphic murine allele of mdm2 to compare the effects of decreased levels of Mdm2 and hence increased p53 activity on tumorigenesis and life span in mice. Here we report that mice with decreased levels of Mdm2 are resistant to tumor formation yet do not age prematurely, supporting the notion that Mdm2 is a promising target for cancer therapeutics.
摘要
p53抑制剂小鼠双微体基因2（Mdm2）是潜在癌症治疗的靶点，然而p53功能增强可能具有致死性。为了直接探究Mdm2功能降低是否能抑制肿瘤发生而不产生有害副作用，我们利用mdm2的一个低表达小鼠等位基因，比较Mdm2水平降低从而p53活性增加对小鼠肿瘤发生和寿命的影响。在此我们报告，Mdm2水平降低的小鼠对肿瘤形成具有抗性，但不会过早衰老，这支持了Mdm2是癌症治疗有前景靶点的观点。
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