Restricted high level expression of Tcf-4 protein in intestinal and mammary gland epithelium
Restricted high level expression of Tcf-4 protein in intestinal and mammary gland epithelium
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DOI：
10.1016/s0002-9440(10)65247-9
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发表时间：
1999-01-01
影响因子：
6
通讯作者：
Clevers, H
中科院分区：
文献类型：
--
作者：
Barker, N;Huls, G;Clevers, H
Tcf-4 是转录因子 Tcf/Lef 家族的成员，在脊椎动物中与 β-catenin 相互作用以介导 Wnt 信号传导。我们之前已经证明，小肠中 APC 的肿瘤抑制功能是通过调节 Tcf-4/β-catenin 转录活性来介导的。为了进一步了解 Tcf-4 在发育和癌变中的作用，我们制备了几种小鼠单克隆抗体，其中一种对 Tcf-4 具有特异性，另一种可识别 Tcf-3 和 Tcf-4。使用 Tcf 4 特异性单克隆抗体进行的免疫组织化学显示，在正常肠和乳腺上皮以及由此衍生的癌中高水平表达。通过 Tcf-3/-4 抗体染色显示，Tcf-3 表达的其他位点仅发生在胃上皮、毛囊和皮肤角质形成细胞内。沿着人小肠上皮的隐窝-绒毛轴观察到时间上的 Tcf-4 表达梯度：强 Tcf-4。表达存在于早期（第 16 周）人胎儿小肠的隐窝内，绒毛几乎检测不到 Tcf-4 蛋白水平，Tcf-4 表达水平在更高度发育（第 22 周）胎儿小肠的绒毛上显着增加。我们得出的结论是，Tcf-4 表现出与肠上皮发育阶段相关的高度受限的表达模式。乳腺上皮和乳腺癌中高水平的 Tcf-4 表达也可能表明在该组织和乳腺癌的发育中发挥作用。
Tcf-4 is a member of the Tcf/Lef family of transcription factors that interact functionally with beta-catenin to mediate Wnt signaling in vertebrates. We have previously demonstrated that the tumor suppressor function of APC in the small intestine is mediated via regulation of Tcf-4/beta-catenin transcriptional activity. To gain further insight into the role of Tcf-4 in development and carcinogenesis we have generated several mouse monoclonal antibodies, one of which is specific for Tcf-4 and another of which recognizes both Tcf-3 and Tcf-4. Immunohistochemistry performed with the Tcf 4-specific monoclonal antibody revealed high levels of expression in normal intestinal and mammary epithelium and carcinomas derived therefrom, Additional sites of Tcf-3 expression, as revealed by staining with the Tcf-3/-4 antibody, occurred only within the stomach epithelium, hair follicles, and keratinocytes of the skin. A temporal Tcf-4 expression gradient was observed along the crypt-villus axis of human small intestinal epithelium: strong Tcf-4. expression was present within the crypts of early (week 16) human fetal small intestine, with the villi showing barely detectable Tcf-4 protein levels, Tcf-4 expression levels increased dramatically on the villi of more highly developed (week 22) fetal small intestine. We conclude that Tcf-4 exhibits a highly restricted expression pattern related to the developmental stage of the intestinal epithelium, The high levels of Tcf-4 expression in mammary epithelium and mammary carcinomas may also indicate a role in the development of this tissue and breast carcinoma.