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

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Abstract
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 β‐catenin, glycogen synthase kinase 3β (GSK‐3β) and Axin/conductin, and induces the degradation of β‐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 β‐catenin) in vitro, destabilizes intracellular β‐catenin, and suppresses β‐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.