Dmp1 is haplo-insufficient for tumor suppression and modifies the frequencies of Arf and p53 mutations in Myc-induced lymphomas
Dmp1 is haplo-insufficient for tumor suppression and modifies the frequencies of Arf and p53 mutations in Myc-induced lymphomas
复制标题
DOI：
10.1101/gad.929901
复制
发表时间：
2001-11-15
影响因子：
10.5
通讯作者：
Sherr, CJ
中科院分区：
文献类型：
--
作者：
Inoue, K;Zindy, F;Sherr, CJ
Dmp1（一种 Arf 转录激活剂）的缺失会导致小鼠自发性肿瘤发生，导致小鼠在两岁时死于各种形式的癌症。野生型 Dmp1 等位基因在 Dmp1(+/-) 小鼠产生的肿瘤中的保留和表达表明，Dmp1 对于肿瘤抑制来说可能是单倍体不足的。 Ep-Myc 诱导的 B 细胞淋巴瘤的平均潜伏期在 Dmp1(-/-) 或 Dmp1(+/-) 遗传背景下减半。尽管 p53 突变或 Arf 缺失通常发生在类似于 50% Ep-Myc 诱导的淋巴瘤中，但 Dmp1 缺失消除了对此类突变的选择，表明 Dmp1 是体内 Arf-p53 途径的有效遗传修饰剂。
Loss of Dmp1, an Arf transcriptional activator, leads to spontaneous tumorigenesis in mice, causing death from various forms of cancer by two years of age. Retention and expression of the wild-type Dmp1 allele in tumors arising in Dmp1(+/-) mice demonstrate that Dmp1 can be haplo-insufficient for tumor suppression. The mean latency of Ep-Myc-induced B-cell lymphomas is halved on a Dmp1(-/-) or Dmp1(+/-) genetic background. Although p53 mutations or Arf deletion normally occur in similar to 50% of Ep-Myc-induced lymphomas, Dmp1 loss obviates selection for such mutations, indicating that Dmp1 is a potent genetic modifier of the Arf-p53 pathway in vivo.