Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/5386
Title
AID-expressing epithelium is protected from oncogenic transformation by an NKG2D surveillance pathway
Author(s)
Perez-Garcia, Arantxa CNIC | Perez-Duran, Pablo CNIC | Wossning, Thomas CNIC | Sernandez, Isora V. | Mur, Sonia M. CNIC | Cañamero, Marta | Real Arribas, Francisco CNIO | Ramiro, Almudena R CNIC
Date issued
2015
Citation
EMBO Mol Med. 2015; 7(10):1327-36
Language
Inglés
Document type
journal article
Abstract
Activation-induced deaminase (AID) initiates secondary antibody
diversification in germinal center B cells, giving rise to higher
affinity antibodies through somatic hypermutation (SHM) or to
isotype-switched antibodies through class switch recombination (CSR).
SHM and CSR are triggered by AID-mediated deamination of cytosines in
immunoglobulin genes. Importantly, AID activity in B cells is not
restricted to Ig loci and can promote mutations and pro-lymphomagenic
translocations, establishing a direct oncogenic mechanism for germinal
center-derived neoplasias. AID is also expressed in response to
inflammatory cues in epithelial cells, raising the possibility that AID
mutagenic activity might drive carcinoma development. We directly tested
this hypothesis by generating conditional knock-in mouse models for AID
overexpression in colon and pancreas epithelium. AID overexpression
alone was not sufficient to promote epithelial cell neoplasia in these
tissues, in spite of displaying mutagenic and genotoxic activity.
Instead, we found that heterologous AID expression in pancreas promotes
the expression of NKG2D ligands, the recruitment of CD8(+) T cells, and
the induction of epithelial cell death. Our results indicate that AID
oncogenic potential in epithelial cells can be neutralized by
immunosurveillance protective mechanisms.
Subject
Activation-induced deaminase | Cancer | Epithelium | NKG2D | Pancreas | INDUCED CYTIDINE DEAMINASE | CLASS SWITCH RECOMBINATION | SINGLE-STRANDED-DNA | ANTIBODY DIVERSIFICATION | SOMATIC HYPERMUTATION | CHROMOSOME TRANSLOCATIONS | GENOMIC INSTABILITY | CANCER DEVELOPMENT | IMMUNE-SYSTEM | C-MYC
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