This report describes familial adenomatous polyposis 1 (FAP1), which is a subtype of familial adenomatous polyposis. The human gene implicated in this disease is APC (Adenomatous Polyposis Coli), which encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. The APC protein is a component of the beta-catenin destruction complex, which regulates Wnt/β-catenin signaling. APC has multiple roles in processes that control cell growth and division and is also implicated in several other types of cancer (see OMIM:611731). There is a second related human gene, APC2; there are also two genes in Drosophila: Dmel\Apc and Dmel\Apc2. Classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for both fly genes.
UAS constructs of the human Hsap\APC gene have been introduced into flies; heterologous rescue has not been tested.
A disease model with flies carrying loss-of-function mutations in both Dmel\Apc and Dmel\Apc2 has been developed; cells in the adult midgut are assayed for epithelial hyperplasia, using somatic clones to produce cells homozygous for mutations in both genes. Candidate genes have been assessed for genetic interactions that modify the disease phenotype. Physical interactions for both Apc and Apc2 protein products have been described; see below and in the FlyBase gene reports for Dmel\Apc and Dmel\Apc2.
Early work assessed the behavior of somatic clones of the Apc-Apc2 double mutant in wing discs; such clones have an overgrowth phenotype which results due to the elimination of surrounding wild-type cells. Somatic clones of the fly Axin gene Axn, a scaffold protein for the beta-catenin destruction complex, exhibit similar overgrowth phenotypes. See the human disease model report 'cancer, multiple, AXIN-related' (FBhh0001045).
[updated May 2019 by FlyBase; FBrf0222196]
Familial adenomatous polyposis (FAP) is a disorder characterized by predisposition to cancer. Affected individuals usually develop hundreds to thousands of adenomatous polyps of the colon and rectum, a small proportion of which will progress to colorectal carcinoma if not surgically treated (Nishisho et al., 1991; pubmed:1651563). [from OMIM:175100; 2016.01.14]
[FAMILIAL ADENOMATOUS POLYPOSIS 1; FAP1](https://omim.org/entry/175100)
[APC REGULATOR OF WNT SIGNALING PATHWAY; APC](https://omim.org/entry/611731)
See description of familial adenomatous polyposis, above.
The APC gene encodes a multidomain protein that plays a major role in tumor suppression by antagonizing the WNT signaling pathway. Inappropriate activation of this pathway through loss of APC function contributes to cancer progression. The APC protein is also an integral part of the beta-catenin signaling pathway. [from OMIM:611731; 2016.01.14]
Ortholog of human genes APC and APC2 (2 Drosophila to 2 human). Dmel\Apc shares 25-26% identity and 37% similarity with both human genes; it lacks a microtubule-binding domain found at the C terminus of the human APC gene.
Ortholog of human genes APC and APC2 (2 Drosophila to 2 human). Dmel\Apc2 is significantly shorter than both human genes and the orthologous fly gene, Dmel\Apc. Dmel\Apc2 shares 26-27% identity and 37-38% similarity with both human genes; it lacks a microtubule-binding domain found at the C terminus of the human APC gene.