title: Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma.
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.
authors.affiliation: Molecular and Cellular Oncogenesis Program, The Wistar Institute, 3601Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Hanlon
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Avila
authors.forename: Renée M
authors.initials: RM
authors.lastname: Demarest
authors.forename: Scott
authors.initials: S
authors.lastname: Troutman
authors.forename: Megan
authors.initials: M
authors.lastname: Allen
authors.forename: Francesca
authors.initials: F
authors.lastname: Ratti
authors.forename: Anil K
authors.initials: AK
authors.lastname: Rustgi
authors.forename: Ben Z
authors.initials: BZ
authors.lastname: Stanger
authors.forename: Fred
authors.initials: F
authors.lastname: Radtke
authors.forename: Volkan
authors.initials: V
authors.lastname: Adsay
authors.forename: Fenella
authors.initials: F
authors.lastname: Long
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Capobianco
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Kissil
mesh_terms: D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D011905:Genes, ras; D051379:Mice; D008822:Mice, Transgenic; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051881:Receptor, Notch1 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495267:CTNNB1 protein, mouse; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D051176:beta Catenin