U19/Eaf2 knockout causes lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostatic intraepithelial neoplasia
U19/Eaf2 knockout causes lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostatic intraepithelial neoplasia
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DOI：
10.1038/sj.onc.1210786
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发表时间：
2008-03-06
期刊：
影响因子：
8
通讯作者：
Wang, Z.
中科院分区：
文献类型：
--
作者：
Xiao, W.;Zhang, Q.;Wang, Z.
上调基因 19 (U19)/ELL 相关因子 2 (Eaf2) 是一种潜在的人类肿瘤抑制因子，在高级别前列腺癌中表现出频繁的等位基因丢失和下调。据报道，U19/Eaf2 及其同源物 Eaf1 可通过与 11-19 富含赖氨酸的白血病 (ELL) 蛋白家族相互作用来调节转录延伸。为了进一步探讨 U19/Eaf2 的肿瘤抑制作用，我们构建并表征了小鼠 U19/Eaf2 敲除模型。 U19/Eaf2的纯合或杂合缺失导致肺腺癌、B细胞淋巴瘤、肝细胞癌和前列腺上皮内瘤变的高发生率。在小鼠前列腺内，U19/Eaf2 缺陷增强了细胞增殖并增加了上皮细胞大小。基因敲除小鼠还表现出心肌细胞肥大。这些数据表明 U19/Eaf2 在生长抑制和细胞大小控制中的作用，并证明 U19/Eaf2 作为多种小鼠组织中的新型肿瘤抑制因子。 U19/Eaf2 敲除小鼠还为三种重要癌症提供了独特的动物模型：肺腺癌、B 细胞淋巴瘤和肝细胞癌。
Upregulated gene 19 (U19)/ELL-associated factor 2 (Eaf2) is a potential human tumor suppressor that exhibits frequent allelic loss and downregulation in high-grade prostate cancer. U19/Eaf2, along with its homolog Eaf1, has been reported to regulate transcriptional elongation via interaction with the eleven-nineteen lysine-rich leukemia (ELL) family of proteins. To further explore the tumor-suppressive effects of U19/Eaf2, we constructed and characterized a murine U19/Eaf2-knockout model. Homozygous or heterozygous deletion of U19/Eaf2 resulted in high rates of lung adenocarcinoma, B-cell lymphoma, hepato cellular carcinoma and prostate intraepithelial neoplasia. Within the mouse prostate, U19/Eaf2 defficiency enhanced cell proliferation and increased epithelial cell size. The knockout mice also exhibited cardiac cell hypertrophy. These data indicate a role for U19/Eaf2 in growth suppression and cell size control as well as argue for U19/Eaf2 as a novel tumor suppressor in multiple mouse tissues. The U19/Eaf2 knockout mouse also provides a unique animal model for three important cancers: lung adenocarcinoma, B-cell lymphoma and hepatocellular carcinoma.