Identification of AF17 As a Downstream Gene of the β-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 β-catenin/T-cell factor pathway. In the experiments reported here, analysis by cDNA microarray indicated that AF17 , a fusion partner of the MLL gene in acute leukemias with t(11;17)(q23;q21), was transactivated according to accumulation of β-catenin. Expression of AF17 was significantly enhanced in 8 of the 12 colorectal cancer tissues examined. Introduction of a plasmid designed to express AF17 stimulated growth of NIH3T3 cells, and fluorescence-activated cell sorter analysis indicated that the AF17 regulation of cell-cycle progression was occurring mainly at the G2-M transition. Our results suggest that the AF17 gene product is likely to be involved in theβ -catenin-T-cell factor/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 acute leukemias by clarifying the pathogenesis of these conditions.