Identification of AF17 as a downstream gene of the beta-catenin/T-cell factor pathway and its involvement in colorectal carcinogenesis

To elucidate the molecular mechanism of colorectal carcinogenesis, we have been attempting to isolate genes involved in the beta -catenin/T-cell facto r pathway. In the experiments reported here, analysis by cDNA microarray in dicated that AF17, a fusion partner of the MLL gene in acute leukemias with t(11;17)(q23;q21), was transactivated according to accumulation of beta -c atenin. Expression of AF17 was significantly enhanced in 8 of the 12 colore ctal cancer tissues examined. Introduction of a plasmid designed to express AF17 stimulated growth of NIH3T3 cells, and fluorescence-activated cell so rter analysis indicated that the AF17 regulation of cell-cycle progression was occurring mainly at the G(2)-M transition. Our results suggest that the AF17 gene product is likely to be involved in the beta -catenin-T-cell fac tor/lymphoid enhancer factor signaling pathway and to function as a growth- promoting, oncogenic protein. These findings should aid development of new strategies for diagnosis, treatment, and prevention of colon cancers and ac ute leukemias by clarifying the pathogenesis of these conditions.