Identification of Sirtuin 3, a mitochondrial protein deacetylase, as a new contributor to tamoxifen resistance in breast cancer cells.
Identification of Sirtuin 3, a mitochondrial protein deacetylase, as a new contributor to tamoxifen resistance in breast cancer cells.
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鉴定出 Sirtuin 3（一种线粒体蛋白脱乙酰酶）是乳腺癌细胞中他莫昔芬耐药性的新贡献者。
DOI：
10.1016/j.bcp.2013.06.032
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发表时间：
2013-09
影响因子：
5.8
通讯作者：
Zhang L, Ren X, Cheng Y, Huber-Keener K, Liu X
中科院分区：
文献类型：
--
作者：
Zhang L, Ren X, Cheng Y, Huber-Keener K, Liu X
目前的研究报告了Sirtuin 3（SIRT 3），一种线粒体蛋白脱乙酰酶，在改变乳腺癌细胞对他莫昔芬（Tam）的敏感性方面的作用，Tam是一种常用的抗雌激素药物。我们发现SIRT 3在Tam耐药的人乳腺癌细胞系MTR-3中在mRNA和蛋白水平上均显著上调，该细胞系是通过在1 μM Tam存在下连续选择性培养MCF-7细胞系两年而获得的。我们进一步证明了SIRT 3在敏感的MCF-7细胞中暴露于Tam后迅速上调。用SIRT 3表达质粒转染MCF-7细胞，降低细胞对Tam的敏感性，并阻断Tam诱导的凋亡。此外，MTR-3细胞中SIRT 3表达的沉默使耐药细胞对Tam敏感并增强凋亡性细胞死亡。SIRT 3基因沉默的MTR-3细胞线粒体ERβ含量增加，ROS水平升高，细胞凋亡增加。这些结果不仅揭示了SIRT 3在癌症中的新作用，而且还确定了这种线粒体蛋白脱乙酰酶是一种以前未被识别的因子，参与了乳腺癌细胞中Tam敏感性的调节。因此，SIRT 3可能被认为是一个潜在的目标，克服Tam耐药的治疗乳腺癌。
The current study reports a previously unappreciated role of Sirtuin 3 (SIRT3), a mitochondrial protein deacetylase, in altering sensitivity of breast cancer cells to tamoxifen (Tam), a commonly used anti-estrogen agent. We showed that SIRT3 was significantly up-regulated at both mRNA and protein levels in the Tam-resistance human breast cancer cell line MTR-3, which was derived from MCF-7 line by continuous selective culture in the presence of 1 μM of Tam for two years. We further demonstrated that SIRT3 was rapidly up-regulated in the sensitive MCF-7 cells following exposure to Tam. Transfection of MCF-7 cells with a SIRT3 expression plasmid decreased cellular sensitivity to Tam and blocked the Tam-induced apoptosis. Furthermore, silencing of SIRT3 expression in MTR-3 cells sensitized the resistant cells to Tam and enhanced apoptotic cell death. MTR-3 cells with silencing of SIRT3 expression showed increases in the mitochondrial content of ERβ, ROS level and apoptosis. These results not only uncovered a new role for SIRT3 in cancer but also identified this mitochondrial protein deacetylase as a previously unrecognized factor that participates in regulation of Tam sensitivity in breast cancer cells. Thus, SIRT3 might be considered as a potential target for overcoming Tam resistance in treatment of breast cancer.
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影响因子：
13.8
作者：
Verdin, Eric;Hirschey, Matthew D.;Finley, Lydia W. S.;Haigis, Marcia C.
通讯作者：
Haigis, Marcia C.
影响因子：
3.7
作者：
Huber-Keener KJ;Liu X;Wang Z;Wang Y;Freeman W;Wu S;Planas-Silva MD;Ren X;Cheng Y;Zhang Y;Vrana K;Liu CG;Yang JM;Wu R
通讯作者：
Wu R
影响因子：
3.7
作者：
Li S;Banck M;Mujtaba S;Zhou MM;Sugrue MM;Walsh MJ
通讯作者：
Walsh MJ
影响因子：
3.9
作者：
Santen, RJ;Song, RX;Yue, W
通讯作者：
Yue, W
雌激素受体-β 评估对接受他莫昔芬辅助治疗的乳腺癌患者的临床重要性
影响因子：
45.3
作者：
Honma N;Horii R;Iwase T;Saji S;Younes M;Takubo K;Matsuura M;Ito Y;Akiyama F;Sakamoto G
通讯作者：
Sakamoto G