AID ‐ expressing epithelium is protected from oncogenic transformation by an NKG2D surveillance pathway by Arantxa Pérez ‐ García, Pablo Pérez ‐ Durán,

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AID ‐ expressing epithelium is protected from oncogenic transformation by an NKG2D surveillance pathway by Arantxa Pérez ‐ García, Pablo Pérez ‐ Durán, Thomas Wossning, Isora V Sernandez, Sonia M Mur, Marta Cañamero, Francisco X Real, and Almudena R Ramiro EMBO Mol Med. Volume ():e August 17, 2015 ©2015 by European Molecular Biology Organization

Inflammation ‐ induced AID expression does not contribute to carcinogenesis A–CAID expression was analyzed in colon and pancreatic human cell lines and in pancreas explants from C57BL/6 mice. Arantxa Pérez ‐ García et al. EMBO Mol Med. doi: /emmm ©2015 by European Molecular Biology Organization

Heterologous AID expression does not promote carcinoma development Schematic of the constructs used for conditional expression of AID in epithelial cells. Arantxa Pérez ‐ García et al. EMBO Mol Med. doi: /emmm ©2015 by European Molecular Biology Organization

Heterologous AID expression does not promote carcinoma development Representative H/E stainings in colonic tissue from 75 ‐ week ‐ old R26AID+/+VillinCRE+/TG (top) and R26AID+/KIVillinCRE+/TG (bottom) mice. Arantxa Pérez ‐ García et al. EMBO Mol Med. doi: /emmm ©2015 by European Molecular Biology Organization

AID expression in pancreas promotes DNA lesions A, BAnalysis of AID mutagenic activity in Elastase1 (A) and Elastase2a (B) by next ‐ generation sequencing. Arantxa Pérez ‐ García et al. EMBO Mol Med. doi: /emmm ©2015 by European Molecular Biology Organization

AID expression in pancreas promotes proliferation and NKG2D ligand expression Representative images of Ki67 staining in pancreas from aged (75 ‐ week ‐ old) R26AID+/+p48CRE+/KI (top) or R26AID+/KIp48CRE+/KI mice (bottom). Arantxa Pérez ‐ García et al. EMBO Mol Med. doi: /emmm ©2015 by European Molecular Biology Organization

Ki67 is expressed in pancreatic epithelial cells Representative immunofluorescence stainings of pancreatic tissue of 20 ‐ week ‐ old R26AID+/KIp48CRE+/KI mice: blue, DAPI; red, Ki67; green, CK8. Arantxa Pérez ‐ García et al. EMBO Mol Med. doi: /emmm ©2015 by European Molecular Biology Organization

AID expression in pancreas promotes immune infiltration and cell death Hematoxylin–eosin (HE) staining of pancreas from aged (75 ‐ week ‐ old) R26AID+/+p48CRE+/KI and R26AID+/KIp48CRE+/KI mice. Arantxa Pérez ‐ García et al. EMBO Mol Med. doi: /emmm ©2015 by European Molecular Biology Organization