Fas/CD95 deficiency in ApcMin/+ mice increases intestinal tumor burden

Hector Guillen-Ahlers, Mark A. Suckow, Francis J. Castellino, Victoria A. Ploplis

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere9070
JournalPloS one
Volume5
Issue number2
DOIs
StatePublished - Feb 5 2010

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