EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer
EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer
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DOI：
10.1093/emboj/cdg542
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发表时间：
2003-10-15
期刊：
影响因子：
11.4
通讯作者：
Helin, K
中科院分区：
文献类型：
--
作者：
Bracken, AP;Pasini, D;Helin, K
最近的实验表明，Polycomb组（PcG）基因EZH2在转移性前列腺癌和淋巴瘤中高度表达。EZH2是PRC2组蛋白甲基转移酶复合体的一个组成部分，该复合体还含有EED和SUZ12，是在胚胎发育过程中沉默HOX基因表达所必需的。在这里，我们证明了EZH2和EED对于转化和非转化的人类细胞的增殖都是必不可少的。此外，pRB-E2F通路严格调控它们的表达，与此一致，我们发现EZH2在大量人类肿瘤中高表达。这些结果提出了一个问题，EZH2是增殖的标志，还是实际上促进了肿瘤的形成。值得注意的是，我们提出EZH2是一个真正的致癌基因，因为我们发现EZH2的异位表达能够为原代细胞提供增殖优势，此外，其基因位点在几种原发肿瘤中被特异性扩增。
Recent experiments have demonstrated that the Polycomb group (PcG) gene EZH2 is highly expressed in metastatic prostate cancer and in lymphomas. EZH2 is a component of the PRC2 histone methyltransferase complex, which also contains EED and SUZ12 and is required for the silencing of HOX gene expression during embryonic development. Here we demonstrate that both EZH2 and EED are essential for the proliferation of both transformed and non-transformed human cells. In addition, the pRB-E2F pathway tightly regulates their expression and, consistent with this, we find that EZH2 is highly expressed in a large set of human tumors. These results raise the question whether EZH2 is a marker of proliferation or if it is actually contributing to tumor formation. Significantly, we propose that EZH2 is a bona fide oncogene, since we find that ectopic expression of EZH2 is capable of providing a proliferative advantage to primary cells and, in addition, its gene locus is specifically amplified in several primary tumors.