Transforming growth factor-β1 is a new form of tumor suppressor with true haploid insufficiency
Transforming growth factor-β1 is a new form of tumor suppressor with true haploid insufficiency
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DOI：
10.1038/nm0798-802
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发表时间：
1998-07-01
期刊：
影响因子：
82.9
通讯作者：
Wakefield, LM
中科院分区：
文献类型：
--
作者：
Tang, BW;Böttinger, EP;Wakefield, LM
转化生长因子β（TGF-β）信号通路的组成部分作为经典的肿瘤抑制因子发挥作用，但TGF-β本身的作用尚不清楚。在这里，我们表明，小鼠TGF-β 1基因的杂合子删除表达只有野生型TGF-β 1蛋白水平的10-30%。虽然大体正常，但这些小鼠具有微妙改变的增殖表型，肝和肺中的细胞更新增加。与野生型同窝小鼠相比，用化学致癌物治疗这些小鼠导致肿瘤发生增强。然而，杂合子小鼠的肿瘤并没有失去剩余的野生型TGF-β 1等位基因，这表明TCF-β 1配体是一种新形式的肿瘤抑制因子，在其防止肿瘤发生的能力方面表现出真正的单倍体不足。
Components of the transforming growth factor-beta (TGF-beta) signal pathway function as classic tumor suppressors, but the role of the TGF-beta s themselves is less clear. Here we show that mice heterozygous for deletion of the TGF-beta 1 gene express only 10-30% of wild-type TGF-beta 1 protein levels. Although grossly normal, these mice have a subtly altered proliferative phenotype, with increased cell turnover in the liver and lung. Treatment of these mice with chemical carcinogens resulted in enhanced tumorigenesis when compared with wild-type littermates. However, tumors in the heterozygous mice did not lose the remaining wild-type TGF-beta 1 allele, indicating that the TCF-beta 1 ligand is a new form of tumor suppressor that shows true haploid insufficiency in its ability to protect against tumorigenesis.