期刊
CANCER CELL
卷 5, 期 2, 页码 163-175出版社
CELL PRESS
DOI: 10.1016/S1535-6108(04)00020-0
关键词
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资金
- NCI NIH HHS [CA29431, R01 CA029431, CA97098, R01 CA097098] Funding Source: Medline
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.
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