Mitochondrial Cytochrome B gene mutation promotes tumor growth in bladder cancer
Mitochondrial Cytochrome B gene mutation promotes tumor growth in bladder cancer
复制标题
DOI：
10.1158/0008-5472.can-07-5532
复制
发表时间：
2008-02-01
期刊：
影响因子：
11.2
通讯作者：
Sidransky, David
中科院分区：
文献类型：
--
作者：
Dasgupta, Santanu;Hoque, Mohammad Obaidul;Sidransky, David
线粒体编码的细胞色素B（CYTB）基因突变在不同的癌症中有报道，但这些突变对细胞代谢和生长的影响尚不清楚。在小鼠异种移植和人膀胱癌模型中，我们显示了CYTB的21-bp缺失突变（mt）过表达的功能效应。mtCYTB的过表达产生了增加的活性氧（ROS），伴随着增加的耗氧量和乳酸产生。MtCYTB过表达通过上调核因子-κ B2信号通路触发快速细胞周期进展，在体外和体内诱导显著的肿瘤生长。肿瘤产生的ROS诱导正常脾细胞的体外裂解。因此，我们提出了一个真正的线粒体基因突变在癌症中的作用的生理和功能的证据。
Mitochondria-encoded Cytochrome B (CYTB) gene mutations were reported in different cancers, but the effect of these mutations on cellular metabolism and growth is unknown. In a murine xenograft and human model of bladder cancer, we show the functional effect of overexpression of a 21-bp deletion mutation (mt) of CYTB. Overexpression of mtCYTB generated increased reactive oxygen species (ROS) accompanied by increased oxygen consumption and lactate production. MtCYTB overexpression induced significant tumor growth in vitro and in vivo by triggering rapid cell cycle progression through up-regulation of the nuclear factor-kappa B2 signaling pathway. Tumor-generated ROS induced in vitro lysis of normal splenocytes. Thus, we present physiologic and functional evidence for the role of a bonafide mitochondrial gene mutation in cancer.