Epiregulin is not essential for development of intestinal tumors but is required for protection from intestinal damage
Epiregulin is not essential for development of intestinal tumors but is required for protection from intestinal damage
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DOI：
10.1128/mcb.24.20.8907-8916.2004
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发表时间：
2004-10-01
影响因子：
5.3
通讯作者：
Threadgill, DW
中科院分区：
文献类型：
--
作者：
Lee, D;Pearsall, RS;Threadgill, DW
表皮调节蛋白是一种表皮生长因子家族成员，作为局部信号介质，具有双重生物学活性，刺激成纤维细胞、肝细胞、平滑肌细胞和角质形成细胞的增殖，同时抑制几种肿瘤来源的上皮细胞系的生长。表皮调节蛋白基因（Ereg）位于小鼠5号染色体上，与其他三个表皮生长因子家族成员epigen、双调蛋白和β细胞素相邻。基因靶向用于将lacZ报告基因插入小鼠Ereg基因座中并消除其功能。尽管epiregulin在空间和时间上广泛表达和调节，但Ereg敲除小鼠没有明显的发育缺陷、生殖异常或肝再生改变。此外，与先前的假设相反，Ereg缺陷不会改变肠癌易感性，如在Apc（Min）模型中测定的，尽管在发展中的肿瘤中显示出稳健的表达。然而，Ereg敲除小鼠对口服葡聚糖硫酸钠引起的癌症易感性肠损伤高度敏感。
Epiregulin, an epidermal growth factor family member, acts as a local signal mediator and shows dual biological activity, stimulating the proliferation of fibroblasts, hepatocytes, smooth muscle cells, and keratinocytes while inhibiting the growth of several tumor-derived epithelial cell lines. The epiregulin gene (Ereg) is located on mouse chromosome 5 adjacent to three other epidermal growth factor family members, epigen, amphiregulin, and betacellulin. Gene targeting was used to insert a lacZ reporter into the mouse Ereg locus and to ablate its function. Although epiregulin is broadly expressed and regulated both spatially and temporally, Ereg null mice show no overt developmental defects, reproductive abnormalities, or altered liver regeneration. Additionally, in contrast to previous hypotheses, Ereg deficiency does not alter intestinal cancer susceptibility, as assayed in the Apc(Min) model, despite showing robust expression in developing tumors. However, Ereg null mice are highly susceptible to cancer-predisposing intestinal damage caused by oral administration of dextran sulfate sodium.