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

被引：128

作者：

Hanlon, Linda ^{[1
]}

Avila, Jacqueline L. ^{[1
]}

Demarest, Renee M. ^{[1
]}

Troutman, Scott ^{[1
]}

Allen, Megan ^{[1
]}

Ratti, Francesca ^{[1
]}

Rustgi, Anil K. ^{[2
,3
]}

Stanger, Ben Z. ^{[2
,3
]}

Radtke, Fred ^{[5
]}

Adsay, Volkan ^{[6
]}

Long, Fenella ^{[4
]}

Capobianco, Anthony J. ^{[1
]}

Kissil, Joseph L. ^{[1
]}

机构：

[1] Wistar Inst Anat & Biol, Mol & Cellular Oncogenesis Program, Philadelphia, PA 19104 USA

[2] Univ Penn, Sch Med, Dept Med, Div Gastroenterol,Abramson Canc Ctr, Philadelphia, PA 19104 USA

[3] Univ Penn, Sch Med, Dept Genet, Div Gastroenterol,Abramson Canc Ctr, Philadelphia, PA 19104 USA

[4] Univ Penn, Fac Pathobiol, Sch Vet Med, Philadelphia, PA 19104 USA

[5] EPFL SV ISREC, Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland

[6] Emory Univ, Sch Med, Atlanta, GA USA

来源：

CANCER RESEARCH | 2010年 / 70卷 / 11期

关键词：

DIFFERENTIATION; TUMORIGENESIS; INACTIVATION; ACTIVATION; CANCER;

D O I：

10.1158/0008-5472.CAN-09-4645

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. Cancer Res; 70(11); 4280-6. (C) 2010 AACR.

引用

页码：4280 / 4286

页数：7

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