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首页> 外文期刊>Cancer Cell >Notch mediates TGF alpha-induced changes in epithelial differentiation during pancreatic tumorigenesis.
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Notch mediates TGF alpha-induced changes in epithelial differentiation during pancreatic tumorigenesis.

机译：Notch介导TGFα诱导的胰腺肿瘤发生过程中上皮分化的变化。

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摘要

Notch signaling regulates cell fate decisions in a wide variety of adult and embryonic tissues. Here we show that Notch pathway components and Notch target genes are upregulated in invasive pancreatic cancer, as well as in pancreatic cancer precursors from both mouse and human. In mouse pancreas, ectopic Notch activation results in accumulation of nestin-positive precursor cells and expansion of metaplastic ductal epithelium, previously identified as a precursor lesion for pancreatic cancer. Notch is also activated as a direct consequence of EGF receptor activation in exocrine pancreas and is required for TGF alpha-induced changes in epithelial differentiation. These findings suggest that Notch mediates the tumor-initiating effects of TG alpha by expanding a population of undifferentiated precursor cells.
机译：Notch信号调节多种成年和胚胎组织中的细胞命运决定。在这里，我们显示，在侵袭性胰腺癌以及来自小鼠和人类的胰腺癌前体中，Notch通路的成分和Notch靶基因均被上调。在小鼠胰腺中，异位Notch激活导致巢蛋白阳性前体细胞积聚和化生性导管上皮细胞的扩增，先前已被确定为胰腺癌的前体病变。 Notch也被激活是外分泌胰腺中EGF受体激活的直接结果，并且是TGFα诱导的上皮分化变化所必需的。这些发现表明，Notch通过扩大未分化的前体细胞群体来介导TG alpha的肿瘤引发作用。

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