Accepted for publication (PostPrint)
K-ras is the most commonly mutated oncogene in pancreatic cancer and its activation in murine models is sufficient to recapitulate the spectrum of lesions seen in human pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that Notch receptor signaling becomes reactivated in a subset of PDACs, leading to the hypothesis that Notch1 functions as an oncogene in this setting. To determine whether Notch1 is required for K-ras-induced tumorigenesis, we used a mouse model in which an oncogenic allele of K-ras is activated and Notch1 is deleted simultaneously in the pancreas. Unexpectedly, the loss of Notch1 in this model resulted in increased tumor incidence and progression, implying that Notch1 can function as a tumor suppressor gene in PDAC.
Hanlon, Linda; Avila, Jacqueline L; Demarest, Renée M; Troutman, Scott; Allen, Megan; Ratti, Francesca; Rustgi, Anil K; Stanger, Ben Z; Radtke, Fred; Adsay, Volkan; Long, Fenella; Capobianco, Anthony J; and Kissil, Joseph L, "Notch1 Functions as a Tumor Suppressor in a Model of K-ras–Induced Pancreatic Ductal Adenocarcinoma" (2010). School of Osteopathic Medicine Faculty Scholarship. 92.
Hanlon L, Avila JL, Demarest RM, Troutman S, Allen M, Ratti F, Rustgi AK, Stanger BZ, Radtke F, Adsay V, Long F, Capobianco AJ, Kissil JL. Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma. Cancer Research. 2010 Jun 1;70(11):4280-6. Epub 2010 May 18. doi: 10.1158/0008-5472.CAN-09-4645. PMID: 20484026. PMCID: PMC2880196.