Sharma Vishva Mitra, Draheim Kyle M, Kelliher Michelle A
Department of Cancer Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Cell Cycle. 2007 Apr 15;6(8):927-30. doi: 10.4161/cc.6.8.4134. Epub 2007 Apr 11.
The Notch receptor family and its ligands (Delta-like and Jagged) have been found deregulated in several human cancers. We and the Aster/Pear group recently identified c-myc as a direct transcriptional target gene of the Notch1 pathway in T cell acute lymphoblastic leukemia (T-ALL). Although the oncogenic roles of c-Myc and Notch1 are established, a direct link between Notch1 and c-Myc had not been demonstrated. Importantly, our work in mouse tal1 tumor cell lines revealed that leukemic growth/survival remains dependent on the Notch1-c-Myc pathway. Studies by the Efstratiadis group provide genetic evidence that the Notch1-c-Myc pathway also contributes to mouse mammary tumorigenesis. Taken together, these studies demonstrate that Notch1 mediates T cell and epithelial cell transformation at least in part by sustaining c-Myc lev.
Notch受体家族及其配体（Delta样和锯齿状）已发现在几种人类癌症中失调。我们和Aster/Pear团队最近在T细胞急性淋巴细胞白血病（T-ALL）中鉴定出c-myc是Notch1通路的直接转录靶基因。虽然c-Myc和Notch1的致癌作用已得到证实，但Notch1与c-Myc之间的直接联系尚未得到证实。重要的是，我们在小鼠tal1肿瘤细胞系中的研究表明，白血病的生长/存活仍然依赖于Notch1-c-Myc通路。Efstratiadis团队的研究提供了遗传学证据，表明Notch1-c-Myc通路也参与小鼠乳腺肿瘤发生。综上所述，这些研究表明Notch1至少部分地通过维持c-Myc水平介导T细胞和上皮细胞转化。
