The Notch1/c-Myc pathway in T cell leukemia.
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.
Sharma
Vishva Mitra
VM
Department of Cancer Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Draheim
Kyle M
KM
Kelliher
Michelle A
MA
D000818:Animals; D053263:Gene Regulatory Networks; D006801:Humans; D015458:Leukemia, T-Cell / Q000235:genetics*; D008954:Models, Biological; D009857:Oncogenes / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology*; D051881:Receptor, Notch1 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
C489427:MYC protein, human; C497761:NOTCH1 protein, human; D016271:Proto-Oncogene Proteins c-myc; D051881:Receptor, Notch1