| First Author | Russell R | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 7677 | PubMed ID | 26220524 |
| Mgi Jnum | J:224440 | Mgi Id | MGI:5662298 |
| Doi | 10.1038/ncomms8677 | Citation | Russell R, et al. (2015) Loss of ATM accelerates pancreatic cancer formation and epithelial-mesenchymal transition. Nat Commun 6:7677 |
| abstractText | Pancreatic ductal adenocarcinoma (PDAC) is associated with accumulation of particular oncogenic mutations and recent genetic sequencing studies have identified ataxia telangiectasia-mutated (ATM) mutations in PDAC cohorts. Here we report that conditional deletion of ATM in a mouse model of PDAC induces a greater number of proliferative precursor lesions coupled with a pronounced fibrotic reaction. ATM-targeted mice display altered TGFbeta-superfamily signalling and enhanced epithelial-to-mesenchymal transition (EMT) coupled with shortened survival. Notably, our mouse model recapitulates many features of more aggressive human PDAC subtypes. Particularly, we report that low expression of ATM predicts EMT, a gene signature specific for Bmp4 signalling and poor prognosis in human PDAC. Our data suggest an intimate link between ATM expression and pancreatic cancer progression in mice and men. |
