Loss of histone H4K20 trimethylation predicts poor prognosis in breast cancer and is associated with invasive activity.
Loss of histone H4K20 trimethylation predicts poor prognosis in breast cancer and is associated with invasive activity.
复制标题
DOI：
10.1186/bcr3681
复制
发表时间：
2014-06-22
期刊：
影响因子：
--
通讯作者：
Matsuura N
中科院分区：
文献类型：
--
作者：
Yokoyama Y;Matsumoto A;Hieda M;Shinchi Y;Ogihara E;Hamada M;Nishioka Y;Kimura H;Yoshidome K;Tsujimoto M;Matsuura N
组蛋白 H4 赖氨酸 20 三甲基化 (H4K20me3) 的缺失与多种癌症相关，但其在乳腺肿瘤中的作用尚不清楚。此外，H4K20me3 整体减少的病理影响仍然大多未知。因此，本研究的一个主要目标是阐明乳腺癌组织中整体H4K20me3水平并探讨其病理功能。通过免疫组织化学在一系列乳腺癌组织中评估 H4K20me3 和相关组蛋白修饰 H3 赖氨酸 9 三甲基化 (H3K9me3) 的水平。进行了单变量和多变量临床病理学和生存分析。我们还检测了组蛋白 H4K20 甲基转移酶 SUV420H1 和 SUV420H2 的过表达或敲低对体外癌细胞侵袭活性的影响。 H4K20me3 在乳腺癌组织中明显减少，但 H3K9me3 没有。 H4K20me3 水平降低与临床病理状态的多个方面相关，包括管腔亚型，但与 HER2 表达无关。多变量分析表明，H4K20me3 水平降低与无病生存率降低独立相关。此外，乳腺癌细胞中SUV420H1和SUV420H2的异位表达抑制了细胞侵袭，而SUV420H2的敲低则在体外激活了正常乳腺上皮细胞的侵袭。与其他类型的肿瘤一样，H4K20me3 在乳腺肿瘤组织的癌变区域中减少。 H4K20me3水平降低可作为乳腺癌患者预后不良的独立标志物。最重要的是，这项研究表明，H4K20me3 水平降低会以不依赖于 HER2 的方式增加乳腺癌细胞的侵袭性。
Loss of histone H4 lysine 20 trimethylation (H4K20me3) is associated with multiple cancers, but its role in breast tumors is unclear. In addition, the pathological effects of global reduction in H4K20me3 remain mostly unknown. Therefore, a major goal of this study was to elucidate the global H4K20me3 level in breast cancer tissue and investigate its pathological functions. Levels of H4K20me3 and an associated histone modification, H3 lysine 9 trimethylation (H3K9me3), were evaluated by immunohistochemistry in a series of breast cancer tissues. Univariate and multivariate clinicopathological and survival analyses were performed. We also examined the effect of overexpression or knockdown of the histone H4K20 methyltransferases, SUV420H1 and SUV420H2, on cancer-cell invasion activity in vitro. H4K20me3, but not H3K9me3, was clearly reduced in breast cancer tissue. A reduced level of H4K20me3 was correlated with several aspects of clinicopathological status, including luminal subtypes, but not with HER2 expression. Multivariate analysis showed that reduced levels of H4K20me3 independently associated with lower disease-free survival. Moreover, ectopic expression of SUV420H1 and SUV420H2 in breast cancer cells suppressed cell invasiveness, whereas knockdown of SUV420H2 activated normal mammary epithelial-cell invasion in vitro. H4K20me3 was reduced in cancerous regions of breast-tumor tissue, as in other types of tumor. Reduced H4K20me3 level can be used as an independent marker of poor prognosis in breast cancer patients. Most importantly, this study suggests that a reduced level of H4K20me3 increases the invasiveness of breast cancer cells in a HER2-independent manner.
登录
查看更多内容
影响因子：
16
作者：
Chandra, Tamir;Kirschner, Kristina;Thuret, Jean-Yves;Pope, Benjamin D.;Ryba, Tyrone;Newman, Scott;Ahmed, Kashif;Samarajiwa, Shamith A.;Salama, Rafik;Carroll, Thomas;Stark, Rory;Janky, Rekin's;Narita, Masako;Xue, Lixiang;Chicas, Agustin;Nunez, Sabrina;Janknecht, Ralf;Hayashi-Takanaka, Yoko;Wilson, Michael D.;Marshall, Aileen;Odom, Duncan T.;Babu, M. Madan;Bazett-Jones, David P.;Tavare, Simon;Edwards, Paul A. W.;Lowe, Scott W.;Kimura, Hiroshi;Gilbert, David M.;Narita, Masashi
通讯作者：
Narita, Masashi
影响因子：
11.5
作者：
Chase, Andrew;Cross, Nicholas C. P.
通讯作者：
Cross, Nicholas C. P.
影响因子：
2
作者：
Behbahani TE;Kahl P;von der Gathen J;Heukamp LC;Baumann C;Gütgemann I;Walter B;Hofstädter F;Bastian PJ;von Ruecker A;Müller SC;Rogenhofer S;Ellinger J
通讯作者：
Ellinger J
影响因子：
11.2
作者：
Elsheikh, Somaia E.;Green, Andrew R.;Ellis, Ian O.
通讯作者：
Ellis, Ian O.
影响因子：
4
作者：
Kourmouli, N;Jeppesen, P;Singh, PB
通讯作者：
Singh, PB