Tumor predisposition in mice mutant for p63 and p73:: Evidence for broader tumor suppressor functions for the p53 family
Tumor predisposition in mice mutant for p63 and p73:: Evidence for broader tumor suppressor functions for the p53 family
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DOI：
10.1016/j.ccr.2005.02.019
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发表时间：
2005-04-01
期刊：
影响因子：
50.3
通讯作者：
Jacks, T
中科院分区：
文献类型：
--
作者：
Flores, ER;Sengupta, S;Jacks, T
p63和p73在功能和结构上与肿瘤抑制因子p53相关。然而，它们自身在肿瘤抑制中的作用尚不清楚。考虑到p63和p73的p53样特性，我们通过所有p53家族基因突变的老龄小鼠检测它们是否参与肿瘤抑制，并对自发性肿瘤进行评分。我们在这里显示p63（+/-）;p73（+/-）小鼠发生自发性肿瘤。p63和p73的缺失也可以与肿瘤发展中的p53缺失协同作用。与p53（+/-）小鼠相比，p53和p63或p53和p73突变杂合的小鼠显示出更高的肿瘤负荷和转移。这些发现为p53家族比以前报道的更广泛的作用提供了证据。
p63 and p73 are functionally and structurally related to the tumor suppressor p53. However, their own role in tumor suppression is unclear. Given the p53-like properties of p63 and p73, we tested whether they are involved in tumor suppression by aging mice heterozygous for mutations in all p53 family genes and scored for spontaneous tumors. We show here that p63(+/-);p73(+/-) mice develop spontaneous tumors. Loss of p63 and p73 can also cooperate with loss of p53 in tumor development. Mice heterozygous for mutations in both p53 and p63 or p53 and p73 displayed higher tumor burden and metastasis compared to p53(+/-) mice. These findings provide evidence for a broader role for the p53 family than has been previously reported.