Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma

Linda Hanlon, Jacqueline L. Avila, Renée M. Demarest, Scott Troutman, Megan Allen, Francesca Ratti, Anil K. Rustgi, Ben Z. Stanger, Fred Radtke, Volkan Adsay, Fenella Long, Anthony J Capobianco, Joseph L. Kissil

Research output: Contribution to journalArticle

100 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4280-4286
Number of pages7
JournalCancer Research
Volume70
Issue number11
DOIs
StatePublished - Jun 1 2010
Externally publishedYes

Fingerprint

Oncogenes
Adenocarcinoma
Notch Receptors
Tumor Suppressor Genes
Pancreatic Neoplasms
Pancreas
Neoplasms
Carcinogenesis
Alleles
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hanlon, L., Avila, J. L., Demarest, R. M., Troutman, S., Allen, M., Ratti, F., ... Kissil, J. L. (2010). Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma. Cancer Research, 70(11), 4280-4286. https://doi.org/10.1158/0008-5472.CAN-09-4645

Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma. / 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; Kissil, Joseph L.

In: Cancer Research, Vol. 70, No. 11, 01.06.2010, p. 4280-4286.

Research output: Contribution to journalArticle

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 2010, 'Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma', Cancer Research, vol. 70, no. 11, pp. 4280-4286. https://doi.org/10.1158/0008-5472.CAN-09-4645
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 ; Kissil, Joseph L. / Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma. In: Cancer Research. 2010 ; Vol. 70, No. 11. pp. 4280-4286.
@article{5c691a13d587471da0a871aa1c152ad1,
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.",
author = "Linda Hanlon and Avila, {Jacqueline L.} and Demarest, {Ren{\'e}e M.} and Scott Troutman and Megan Allen and Francesca Ratti and Rustgi, {Anil K.} and Stanger, {Ben Z.} and Fred Radtke and Volkan Adsay and Fenella Long and Capobianco, {Anthony J} and Kissil, {Joseph L.}",
year = "2010",
month = "6",
day = "1",
doi = "10.1158/0008-5472.CAN-09-4645",
language = "English",
volume = "70",
pages = "4280--4286",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "11",

}

TY - JOUR

T1 - Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma

AU - Hanlon, Linda

AU - Avila, Jacqueline L.

AU - Demarest, Renée M.

AU - Troutman, Scott

AU - Allen, Megan

AU - Ratti, Francesca

AU - Rustgi, Anil K.

AU - Stanger, Ben Z.

AU - Radtke, Fred

AU - Adsay, Volkan

AU - Long, Fenella

AU - Capobianco, Anthony J

AU - Kissil, Joseph L.

PY - 2010/6/1

Y1 - 2010/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77953158971&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953158971&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-09-4645

DO - 10.1158/0008-5472.CAN-09-4645

M3 - Article

C2 - 20484026

AN - SCOPUS:77953158971

VL - 70

SP - 4280

EP - 4286

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 11

ER -