Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues
Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues
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DOI：
10.1016/j.cell.2005.02.018
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发表时间：
2005-05-06
期刊：
影响因子：
64.5
通讯作者：
Jaenisch, R
中科院分区：
文献类型：
--
作者：
Hochedlinger, K;Yamada, Y;Jaenisch, R
POU 结构域转录因子 Oct-4 通常在哺乳动物胚胎的多能细胞中表达。此外，生殖细胞肿瘤和一些体细胞肿瘤显示出可检测到的 Oct-4 表达。虽然 Oct-4 在植入前发育过程中的作用是维持胚胎细胞处于多能状态，但对其潜在的致癌特性知之甚少。在这里，我们使用强力霉素依赖性表达系统研究异位 Oct-4 表达对成年小鼠体组织的影响。 Oct-4 的激活会导致上皮组织发育异常，而这种生长依赖于 Oct-4 的持续表达。发育异常病变显示祖细胞扩张和β-连环蛋白转录活性增加。在肠道中，Oct-4 表达通过抑制细胞分化而导致发育不良，其方式与胚胎细胞中类似。这些数据表明，某些成年祖细胞仍然有能力解释关键的胚胎信号，并支持祖细胞是肿瘤发生驱动力的观点。
The POU-domain transcription factor Oct-4 is normally expressed in pluripotent cells of the mammalian embryo. In addition, germ-cell tumors and a few somatic tumors show detectable expression of Oct-4. While Oct-4's role during preimplantation development is to maintain embryonic cells in a pluripotent state, little is known about its potential oncogenic properties. Here we investigate the effect of ectopic Oct-4 expression on somatic tissues of adult mice using a doxycycline-dependent expression system. Activation of Oct-4 results in dysplastic growths in epithelial tissues that are dependent on continuous Oct-4 expression. Dysplastic lesions show an expansion of progenitor cells and increased beta-catenin transcriptional activity. In the intestine, Oct-4 expression causes dysplasia by inhibiting cellular differentiation in a manner similar to that in embryonic cells. These data show that certain adult progenitors remain competent to interpret key embryonic signals and support the notion that progenitor cells are a driving force in tumorigenesis.