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NDRG2 promotes adriamycin sensitivity through a Bad/p53 complex at the mitochondria in breast cancer.

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机构: [1]State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi’an, 710032, Shaanxi, China [2]Department of Pathology, The Fourth Military Medical University, Xi’an, 710032, Shaanxi, China [3]Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, 310058, Hangzhou, China [4]Department of Oncology, The State Key Discipline of Cell Biology, Xijing Hospital, The Fourth Military Medical University, Xi’an, 710032, Shaanxi, China [5]Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, 710038, Xi’an, China [6]College of Life Science, Sichuan University, Chendu, 610065, Sichuan, China [7]Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi’an, 710032, Shaanxi, China
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Chemo-resistance presents a difficult challenge for the treatment of breast cancer. Our previous study showed that N-Myc downstream-regulated gene 2 (NDRG2) is involved in p53-mediated apoptosis induced by chemotherapy, through a mechanism that has so far remained obscure. Here, we explored the role of NDRG2 in chemo-resistance with a focus on Adriamycin (ADR) and found that NDRG2 expression decreased in ADR resistance breast cancer cells. Interestingly, NDRG2 can promote ADR sensitivity by inhibiting proliferation, enhancing cellular damage responses, and promoting apoptosis in a p53-dependent manner. We also found that NDRG2 could upregulate Bad expression by increasing its half-life, which is associated with p53 to mitochondria. Hence, our collective data provided the first evidence that NDRG2 promoting sensitivity of breast cancer is dependent on p53 by preventing p53 from entering the nucleus rather than changing its expression.

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出版当年[2017]版:
大类 | 2 区 医学
小类 | 2 区 肿瘤学 3 区 细胞生物学
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第一作者机构: [1]State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi’an, 710032, Shaanxi, China
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通讯机构: [1]State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi’an, 710032, Shaanxi, China [7]Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi’an, 710032, Shaanxi, China
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