Our work has shown that the transcription factor Myb/MYB is essential to maintain stem/progenitor cell homesostasis in epithelium such as the skin, breast and intestine. Myb is over-expressed in most breast and colorectal cancer (CRC). In fact Myb is a poor prognosis marker in CRC and patients among whom the ones with highest Myb are more likely to relapse. We investigated whether Myb the reason why is such a poor prognosis indicator.
To mimic CRC patients with high Myb expression, we generated the first intestinal-specific, inducible transgenic model for Myb and activated Myb during CRC initiation using a pro-carcinogen treatment, azoxymethane (AOM). As a result of Myb activation most measured aspects of colon stem cell gene expression and function were exacerbated and tumorigenesis was accelerated. CRC-associated symptoms of patients including intestinal bleeding and anemia were faithfully mimicked in our transgenic identifying an additional pathogenic role for Myb. We are now investigating how Myb promotes CRC through the modulation of target genes such as CyclinE1.
Our work suggests that Myb has a driver role in CRC and provides clues to unravel the many faces of Myb in cancer to understand why patients with low Myb expression do better than those with high Myb expression.