Identification and characterization of E-APC, a novel Drosophila homologue of the tumour suppressor APC

Background: Mutations in the adenomatous polyposis coli (APC) tumour suppressor gene are implicated in the genesis of colorectal cancers, The product of the APC gene forms a complex with beta-catenin, glycogen synthase kinase 3 beta (GSK-3 beta) and Axin/conductin, and induces the degradation of beta-catenin. Results: We have identified a novel Drosophila homologue of APC, E-APC, which is similar to but differs in several respects from D-APC, The E-APC cDNA encodes a protein of predicted 1067 amino acids, with seven armadillo repeats, two copies of the 15-amino acid repeat, five copies of the 20-amino acid repeat, and one Axin/conductin binding site, E-APC directly interacts with D-Axin and Armadillo (Arm, the Drosophila homologue of beta-catenin) in vitro, destabilizes intracellular beta-catenin, and suppresses beta-catenin/TCF-regulated transcription in APC(-/-) colon cancer cells, The E-APC mRNA is ubiquitously expressed throughout all developmental stages in Drosophila. Conclusion: Our findings suggest that E-APC may be universally involved in the regulation of the Wingless signalling pathway by down-regulating the level of Arm in Drosophila.