| First Author | Guillen-Ahlers H | Year | 2010 |
| Journal | PLoS One | Volume | 5 |
| Issue | 2 | Pages | e9070 |
| PubMed ID | 20140201 | Mgi Jnum | J:158010 |
| Mgi Id | MGI:4437517 | Doi | 10.1371/journal.pone.0009070 |
| Citation | Guillen-Ahlers H, et al. (2010) Fas/CD95 deficiency in ApcMin/+ mice increases intestinal tumor burden. PLoS One 5(2):e9070 |
| abstractText | 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/+)/Fas(lpr)) by cross-breeding Apc(Min/+) mice with Fas deficient (Fas(lpr)) mice. One of the main limitations of the Apc(Min/+) mouse model is that it only develops benign polyps. However, Apc(Min/+)/Fas(lpr) mice presented with a dramatic increase in tumor burden relative to Apc(Min/+) 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 Apc(Min/+)/Fas(lpr) mice relative to Apc(Min/+) cohorts, which resulted in enhanced inflammation. CONCLUSIONS/SIGNIFICANCE: This study demonstrated that imposition of a Fas deletion in an Apc(Min/+) background results in a more aggressive phenotype of the Apc(Min/+) mouse model, with more rapid development of invasive intestinal tumors and a decrease in Fas-L levels. |
