EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells
EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells
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DOI：
10.1073/pnas.1933744100
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发表时间：
2003-09-30
影响因子：
11.1
通讯作者：
Chinnaiyan, AM
中科院分区：
文献类型：
--
作者：
Kleer, CG;Cao, Q;Chinnaiyan, AM
Polycomb Group蛋白EZH2是一种参与控制细胞记忆的转录抑制因子，与侵袭性前列腺癌有关。在这里，我们研究EZH2在癌细胞侵袭和乳腺癌进展中的功能作用。与正常乳腺上皮相比，浸润性乳腺癌中EZH2的转录和蛋白质持续升高。包括来自280名患者的917个样本的组织微阵列分析表明，EZH2蛋白水平与乳腺癌的侵袭性密切相关。永生化人乳腺上皮细胞系中EZH2的过表达促进非贴壁依赖性生长和细胞侵袭。EZH2介导的细胞侵袭需要完整的SET结构域和组蛋白脱乙酰酶活性。这项研究提供了令人信服的证据失调的细胞记忆，转录抑制和肿瘤转化之间的功能联系。
The Polycomb Group Protein EZH2 is a transcriptional repressor involved in controlling cellular memory and has been linked to aggressive prostate cancer. Here we investigate the functional role of EZH2 in cancer cell invasion and breast cancer progression. EZH2 transcript and protein were consistently elevated in invasive breast carcinoma compared with normal breast epithelia. Tissue microarray analysis, which included 917 samples from 280 patients, demonstrated that EZH2 protein levels were strongly associated with breast cancer aggressiveness. Overexpression of EZH2 in immortalized human mammary epithelial cell lines promotes anchorage-independent growth and cell invasion. EZH2-mediated cell invasion required an intact SET domain and histone deacetylase activity. This study provides compelling evidence for a functional link between dysregulated cellular memory, transcriptional repression, and neoplastic transformation.