Notch1 Functions as a Tumor Suppressor in a Model of K-ras–Induced Pancreatic Ductal Adenocarcinoma

Authors

Linda Hanlon, University of Pennsylvania
Jacqueline L Avila, University of Pennsylvania
Renée M Demarest, Rowan University
Scott Troutman, University of Pennsylvania
Megan Allen, University of Pennsylvania
Francesca Ratti, University of Pennsylvania
Anil K Rustgi, University of Pennsylvania
Ben Z Stanger, University of Pennsylvania
Fred Radtke, Ecole Polytechnique Federale de Lausanne
Volkan Adsay, Emory University
Fenella Long, University of Pennsylvania
Anthony J Capobianco, University of Pennsylvania
Joseph L Kissil, University of Pennsylvania

Document Type

Article

Version Deposited

Accepted for publication (PostPrint)

Publication Date

6-1-2010

Publication Title

Cancer Research

DOI

10.1158/0008-5472.CAN-09-4645

Abstract

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.

Comments

This manuscript has been accepted for publication in Cancer Research, which is published by the American Association for Cancer Research. The publisher's final edited version of this article is available free at Cancer Research.

Recommended Citation

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.