Background: Fas, a member of the tumor necrosis family, is responsible for initiating the apoptotic pathway when bound to its ligand, Fas-L. Defects in the Fas-mediated apoptotic pathway have been reported in colorectal cancer. Methodology/Principal Findings: In the present study, a variant of the Apc Min/+ mouse, a model for the human condition, Familial Adenomatous Polyposis (FAP), was generated with an additional deficiency of Fas (Apc Min/+/Faslpr) by crossbreeding ApcMin/+ mice with Fas deficient (Faslpr) mice. One of the main limitations of the Apc Min/+ mouse model is that it only develops benign polyps. However, ApcMin/+/Faslpr mice presented with a dramatic increase in tumor burden relative to ApcMin/+ mice and invasive lesions at advanced ages. Proliferation and apoptosis markers revealed an increase in cellular proliferation, but negligible changes in apoptosis, while p53 increased at early ages. Fas-L was lower in ApcMin/+/Faslpr mice relative to ApcMin/+ cohorts, which resulted in enhanced inflammation. Conclusions/Significance: This study demonstrated that imposition of a Fas deletion in an ApcMin/+ background results in a more aggressive phenotype of the ApcMin/+ mouse model, with more rapid development of invasive intestinal tumors and a decrease in Fas-L levels. © 2010 Guillen-Ahlers et al.
Guillen-Ahlers, H., Suckow, M. A., Castellino, F. J., & Ploplis, V. A. (2010). Fas/CD95 deficiency in ApcMin/+ mice increases intestinal tumor burden. PLoS ONE, 5(2). https://doi.org/10.1371/journal.pone.0009070