The methyltransferase EZH2 is not required for mammary cancer development, although high EZH2 and low H3K27me3 correlate with poor prognosis of ER-positive breast cancers.
The methyltransferase EZH2 is not required for mammary cancer development, although high EZH2 and low H3K27me3 correlate with poor prognosis of ER-positive breast cancers.
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DOI：
10.1002/mc.22188
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发表时间：
2015-10
影响因子：
4.6
通讯作者：
Hennighausen, Lothar
中科院分区：
文献类型：
--
作者：
Bae, Woo Kyun;Yoo, Kyung Hyun;Lee, Ji Shin;Kim, Young;Chung, Ik-Joo;Park, Min Ho;Yoon, Jung Han;Furth, Priscilla A.;Hennighausen, Lothar
zeste同源物2增强子（EZH 2）催化组蛋白H3赖氨酸27（H3 K27 me 3）的三甲基化，并且其去甲基化由UTX催化。EZH 2水平在乳腺癌中经常升高，并且已经提出通过调节抑制性H3 K27 me 3标记来控制基因表达。然而，尚未完全确定具有不同水平的H3 K27 me 3、EZH 2和UTX的乳腺癌是否表现出不同的生物学行为。在146例乳腺癌中评估H3 K27 me 3、EZH 2和UTX的水平及其预后意义。HER 2阴性样本中H3 K27 me 3水平较高。EZH 2在LN+、大小> 20 mm、肿瘤分级和分期较高的癌症中表达较高。使用考克斯回归模型，H3 K27 me 3水平和EZH 2表达被确定为所有研究的乳腺癌以及ER阳性亚组的总生存期的独立预后因素。低H3 K27 me 3和高EZH 2表达水平的组合与较短的生存期显著相关。UTX表达与预后无明显相关性，H3 K27 me 3与EZH 2/UTX表达无相关性。为了确定在乳腺癌中建立H3 K27 me 3标记是否需要EZH 2，在小鼠的乳腺干细胞中缺失Brca 1和EZH 2。H3 K27 me 3水平不变的Brca 1缺陷型乳腺癌在EZH 2不存在的情况下发生，表明EZH 2不是乳腺瘤形成中的强制性H3 K27甲基转移酶，并为该组织中H3 K27 me 3和EZH 2之间的生物学独立性提供遗传证据。
Enhancer of zeste homolog 2 (EZH2) catalyzes trimethylation of histone H3 lysine 27 (H3K27me3) and its demethylation is catalyzed by UTX. EZH2 levels are frequently elevated in breast cancer and have been proposed to control gene expression through regulating repressive H3K27me3 marks. However, it is not fully established whether breast cancers with different levels of H3K27me3, EZH2 and UTX exhibit different biological behaviors. Levels of H3K27me3, EZH2 and UTX and their prognostic significance were evaluated in one hundred forty six (146) cases of breast cancer. H3K27me3 levels were higher in HER2-negative samples. EZH2 expression was higher in cancers that were LN+, size > 20mm, and with higher tumor grade and stage. Using a Cox regression model, H3K27me3 levels and EZH2 expression were identified as independent prognostic factors for overall survival for all the breast cancers studied as well as the ER-positive subgroup. The combination of low H3K27me3 and high EZH2 expression levels were significantly associated with shorter survival. UTX expression was not significantly associated with prognosis and there were no correlations between H3K27me3 levels and EZH2/UTX expression. To determine if EZH2 is required to establish H3K27me3 marks in mammary cancer, Brca1 and Ezh2 were deleted in mammary stem cells in mice. Brca1-deficient mammary cancers with unaltered H3K27me3 levels developed in the absence of EZH2, demonstrating that EZH2 is not a mandatory H3K27 methyltransferase in mammary neoplasia and providing genetic evidence for biological independence between H3K27me3 and EZH2 in this tissue.
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影响因子：
2.5
作者：
Ko, Seung Sang
通讯作者：
Ko, Seung Sang
影响因子：
6.6
作者：
Holm, Karolina;Grabau, Dorthe;Ringner, Markus
通讯作者：
Ringner, Markus
DOI：
10.1084/jem.20131144
发表时间：
2013-11-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Muto T;Sashida G;Oshima M;Wendt GR;Mochizuki-Kashio M;Nagata Y;Sanada M;Miyagi S;Saraya A;Kamio A;Nagae G;Nakaseko C;Yokote K;Shimoda K;Koseki H;Suzuki Y;Sugano S;Aburatani H;Ogawa S;Iwama A
通讯作者：
Iwama A
影响因子：
12.3
作者：
Herschkowitz JI;Simin K;Weigman VJ;Mikaelian I;Usary J;Hu Z;Rasmussen KE;Jones LP;Assefnia S;Chandrasekharan S;Backlund MG;Yin Y;Khramtsov AI;Bastein R;Quackenbush J;Glazer RI;Brown PH;Green JE;Kopelovich L;Furth PA;Palazzo JP;Olopade OI;Bernard PS;Churchill GA;Van Dyke T;Perou CM
通讯作者：
Perou CM
影响因子：
5.7
作者：
Cai, Mu-Yan;Tong, Zhu-Ting;Xie, Dan
通讯作者：
Xie, Dan