Notch介导胰腺肿瘤发生过程中TGFα诱导的上皮分化变化。
Notch mediates TGF alpha-induced changes in epithelial differentiation during pancreatic tumorigenesis.
作者信息
Miyamoto Yoshiharu, Maitra Anirban, Ghosh Bidyut, Zechner Ulrich, Argani Pedram, Iacobuzio-Donahue Christine A, Sriuranpong Virote, Iso Tatsuya, Meszoely Ingrid M, Wolfe Michael S, Hruban Ralph H, Ball Douglas W, Schmid Roland M, Leach Steven D
机构信息
Departments of Surgery, Oncology, and Pathology, The Sidney Kimmel Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
出版信息
Cancer Cell. 2003 Jun;3(6):565-76. doi: 10.1016/s1535-6108(03)00140-5.
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.
Notch信号通路在多种成年和胚胎组织中调节细胞命运决定。我们在此表明，Notch信号通路成分和Notch靶基因在侵袭性胰腺癌以及来自小鼠和人类的胰腺癌前体中上调。在小鼠胰腺中，异位Notch激活导致巢蛋白阳性前体细胞积累和化生导管上皮扩张，化生导管上皮先前被确定为胰腺癌的前体病变。Notch也是外分泌胰腺中表皮生长因子受体激活的直接后果，并且是转化生长因子α诱导的上皮分化变化所必需的。这些发现表明，Notch通过扩大未分化前体细胞群体介导转化生长因子α的肿瘤起始作用。
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