This report encompasses a series of multigenic models of colorectal cancer, using combinations of Drosophila genes related to 5 human genes implicated in this disease: human NRAS (using an activated form of Dmel\Ras85D), human TP53 (using RNAi-knockdown targeted to Dmel\p53), human APC (using RNAi-knockdown targeted to Dmel\Apc), human PIK3CA (using RNAi-knockdown targeted to Dmel\Pten, a negative regulator of the PIK3 signaling pathway), and human SMAD4 (using RNAi-knockdown targeted to Dmel\Med). Multigenic combinations were created in the adult hindgut epithelium using GAL4 driven by the hindgut-specific byn promoter. 32 different combinations that correspond those found in colorectal human tumors have been characterized; mechanisms of drug resistance have been investigated.
See also human disease model reports for 'colorectal cancer' (FBhh0000178), 'cancer, multiple, RAS-related' (FBhh0000474), 'cancer, multiple, TP53-related' (FBhh0000340), 'cancer, multiple, PIK3C-related' (FBhh0000400), 'familial adenomatous polyposis 1' (FBhh0000135).
[updated Nov. 2017 by FlyBase; FBrf0222196]
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.