Apc encodes the adenomatosis polyposis coli protein with diverse cellular functions including cellular proliferation, differentiation, cytoskeleton regulation, migration and apoptosis. APC mutations are commonly associated with intestinal tumorigenesis, and increasingly implicated with phenotypes outside of the intestine.
The hypomorphic mutation Apc1572T is designed to have stable expression of a truncated protein (Apc1572) that results in constitutive activation of the Wnt/β-catenin signal transduction pathway. The phenotype of Apc1572T mice on a C57BL/6 genetic background are described below.
All homozygous mice (Apc1572T/1572T) are embryonic lethal. Heterozygous mice (Apc1572T/+) are a model of Wnt-driven, metaplastic mammary adenocarcinoma; a subtype of triple-negative breast cancer (TNBC). Apc1572T/+ exhibit intermediate levels of Wnt/β-catenin signaling activation, resulting in highly-penetrant, multifocal mammary adenocarcinomas (virgin females [100%] and males [30%]), with subsequent pulmonary metastases in both female and male mice. Notably, the histology of the primary mammary tumors in Apc1572T/+ animals is highly heterogeneous with luminal, myoepithelial and squamous lineages, reminiscent of metaplastic carcinoma of the breast, a rare TNBC subtype characterized by an admixture of adenocarcinoma with areas of squamous, spindle cell and/or mesenchymal phenotype. Heterozygous females develop breast tumors beginning ~8 weeks of age. Some of the heterozygous males may also develop breast tumors. No increased susceptibility to spontaneous intestinal adenomas are reported for heterozygotes.
These Apc1572T mice may also be useful for isolating a subpopulation of mammary cancer stem cells (MaCSCs) that are capable of self-renewal and differentiation both in vivo and in vitro.
The donating investigator reports they observe no significant incidence of liver tumors in Apc1572T/+ (July 2016).
