Metallothionein 1 h tumour suppressor activity in prostate cancer is mediated by euchromatin methyltransferase 1.
Metallothionein 1 h tumour suppressor activity in prostate cancer is mediated by euchromatin methyltransferase 1.
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DOI：
10.1002/path.4169
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发表时间：
2013-06
影响因子：
7.3
通讯作者：
Luo, Jian-Hua
中科院分区：
文献类型：
--
作者：
Han, Yu-Chen;Zheng, Zhong-Liang;Zuo, Ze-Hua;Yu, Yan P.;Chen, Rui;Tseng, George C.;Nelson, Joel B.;Luo, Jian-Hua
金属硫蛋白（MT）是一组金属结合蛋白，被认为在重金属解毒中发挥作用。在这里，我们通过微阵列和验证分析表明，MT的成员MT1h在许多人类恶性肿瘤中下调。MT1h的低表达与前列腺癌和肝癌的不良临床结局相关。我们发现MT1h的启动子区域在癌症中是高甲基化的，MT1h启动子的去甲基化逆转了MT1h表达的抑制。MT1h的强制表达诱导细胞生长停滞，抑制集落形成，延缓迁移，并减少侵袭。与未诱导的对照组相比，具有可诱导MT1h表达的肿瘤异种移植物的SCID小鼠具有较低的肿瘤体积以及较少的转移和死亡。MT1h被发现与常染色质组蛋白甲基转移酶1（EHMT1）相互作用，并增强其对组蛋白3的甲基转移酶活性。敲除EHMT 1或MT 1h中的突变消除了其与EHMT 1的相互作用，从而消除了MT 1h的肿瘤抑制活性。这证明了依赖于组蛋白甲基化激活的重金属结合蛋白的肿瘤抑制活性。
Metallothioneins (MTs) are a group of metal binding proteins thought to play a role in the detoxification of heavy metals. Here we showed by microarray and validation analyses that MT1h, a member of MT, is down-regulated in many human malignancies. Low expression of MT1h was associated with poor clinical outcomes in both prostate and liver cancer. We found that the promoter region of MT1h was hypermethylated in cancer and that demethylation of the MT1h promoter reversed the suppression of MT1h expression. Forced expression of MT1h induced cell growth arrest, suppressed colony formation, retarded migration, and reduced invasion. SCID mice with tumour xenografts with inducible MT1h expression had lower tumour volumes as well as fewer metastases and deaths than uninduced controls. MT1h was found to interact with euchromatin histone methyltransferase 1 (EHMT1) and enhanced its methyltransferase activity on histone 3. Knocking down of EHMT1 or a mutation in MT1h that abrogates its interaction with EHMT1 abrogated MT1h tumour suppressor activity. This demonstrates tumour suppressor activity in a heavy metal binding protein that is dependent on activation of histone methylation.
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影响因子：
8
作者：
Ren, B;Yu, G;Luo, JH
通讯作者：
Luo, JH
影响因子：
4.2
作者：
Tang, XH;Shay, NF
通讯作者：
Shay, NF
影响因子：
6
作者：
Yu, GY;Tseng, GC;Luo, JH
通讯作者：
Luo, JH
组蛋白赖氨酸甲基化对人脑焦点的表观遗传调节。
影响因子：
10.6
作者：
Akbarian, Schahram;Huang, Hsien-Sung
通讯作者：
Huang, Hsien-Sung
DOI：
10.1093/jnci/djk199
发表时间：
2007-06-06
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Ren, Baoguo;Yu, Yan P.;Luo, Jian-Hua
通讯作者：
Luo, Jian-Hua