Intestinal adenoma formation and MYC activation are regulated by cooperation between MYB and Wnt signaling
D Ciznadija, R Tothill, ML Waterman, L Zhao, D Huynh, RM Yu, M Ernst, S Ishii, T Mantamadiotis, TJ Gonda, RG Ramsay, J Malaterre
CELL DEATH AND DIFFERENTIATION | NATURE PUBLISHING GROUP | Published : 2009
Aberrant Wnt signaling mediated by mutations affecting APC (adenomatous polyposis coli) or beta-catenin initiates the majority of human colorectal cancers (CRC) and drives tumorigenesis through the activation of specific genes such as MYC. We report here a novel association whereby another oncogenic transcription factor, MYB/c-Myb, is necessary for intestinal adenoma development directed by activated Wnt signaling. APC(Min/+) mice in which c-myb is haploinsufficient survive longer than wild-type APC(Min/+) animals due to a delay in adenoma formation. Intestinal adenomas from APC(Min/+) mice were assessed and found to have high levels of c-myc gene expression. We explored the relationship bet..View full abstract
This work was supported by a fellowship (RGR) and grants from the NHMRC, Australia. We thank Alla Mirochnik and Tony Li (Department of Microbiology and Department of Molecular Genetics, University of California, Irvine, CA, USA) for the generous provision of reagents and time. Suggestions by Dr. Ross Hannan were also of great assistance during the preparation of the paper.