Human MUC1 carcinoma-associated protein confers resistance to genotoxic anticancer agents
Human MUC1 carcinoma-associated protein confers resistance to genotoxic anticancer agents
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DOI：
10.1016/s1535-6108(04)00020-0
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发表时间：
2004-02-01
期刊：
影响因子：
50.3
通讯作者：
Kufe, D
中科院分区：
文献类型：
--
作者：
Ren, J;Agata, N;Kufe, D
MUC 1转化蛋白在大多数人类肿瘤中过表达。目前的研究表明，MUC 1C-末端亚基（MUC 1 C-ter）定位于HCT 116/MUC 1结肠癌细胞的线粒体，并且heregulin刺激MUC 1 C-ter的线粒体靶向。我们还发现MUC 1减弱顺铂诱导的（1）线粒体促凋亡因子的释放，（2）caspase-3的激活，和（3）诱导细胞凋亡。此外，MUC 1 siRNA敲低A549肺癌和ZR-75-1乳腺癌细胞中MUC 1表达与体外和体内对遗传毒性药物的敏感性增加相关。这些研究结果表明，MUC 1减弱DNA损伤的凋亡反应，这种癌蛋白赋予耐药基因毒性抗癌剂。
The MUC1 transforming protein is overexpressed by most human carcinomas. The present studies demonstrate that the MUC1C-terminal subunit (MUC1 C-ter) localizes to mitochondria in HCT116/MUC1 colon carcinoma cells and that heregulin stimulates mitochondrial targeting of MUC1 C-ter. We also show that MUC1 attenuates cisplatin-induced (1) release of mitochondrial apoptogenic factors, (2) activation of caspase-3, and (3) induction of apoptosis. Moreover, knockdown of MUC1 expression in A549 lung and ZR-75-1 breast carcinoma cells by MUC1 siRNA was associated with increased sensitivity to genotoxic drugs in vitro and in vivo. These findings indicate that MUC1 attenuates the apoptotic response to DNA damage and that this oncoprotein confers resistance to genotoxic anticancer agents.