Tgfbr1 Haploinsufficiency Inhibits the Development of Murine Mutant Kras-Induced Pancreatic Precancer

被引：23

作者：

Adrian, Kevin

Strouch, Matthew J.

Zeng, Qinghua ^{[3
,4
]}

Barron, Morgan R.

Cheon, Eric C. ^{[5
]}

Honasoge, Akilesh

Xu, Yanfei ^{[2
]}

Phukan, Sharbani ^{[2
]}

Sadim, Maureen ^{[2
]}

Bentrem, David J.

Pasche, Boris ^{[3
,4
]}

Grippo, Paul J. ^{[1
]}

机构：

[1] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Dept Surg, Chicago, IL 60611 USA

[2] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Hematol Oncol,Canc Genet Program, Chicago, IL 60611 USA

[3] Univ Alabama, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA

[4] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA

[5] Univ Illinois, Dept Surg, Mt Sinai Hosp, Chicago, IL 60680 USA

来源：

CANCER RESEARCH | 2009年 / 69卷 / 24期

关键词：

DUCTAL ADENOCARCINOMA; COLORECTAL-CANCER; TUMOR SUPPRESSION; BETA RECEPTORS; EXPRESSION; SMAD4; PROGRESSION; ACTIVATION; PROGNOSIS; NEOPLASIA;

D O I：

10.1158/0008-5472.CAN-09-1705

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

To dissect the role of constitutively altered Tgfbr1 signaling in pancreatic cancer development, we crossed Elastase-Kras(G12D) (EL-Kras) mice with Tgfbr1 haploinsufficient mice to generate EL-Kras/Tgfbr1(+/-) mice. Mice were euthanized at 6 to 9 months to compare the incidence, frequency, and size of precancerous lesions in the pancreas. Only 50% of all EL-Kras/Tgfbr1(+/-) mice developed preinvasive lesions compared with 100% of EL-Kras (wild-type Tgfbr1) mice. The frequency of precancerous lesions was 4-fold lower in haploinsufficient than in control mice. Paradoxically, the precancerous lesions of EL-Kras/Tgfbr1(+/-) mice were considerably larger than those in EL-Kras mice. Yet, the mitotic index of precancerous cells and the observable levels of fibrosis, lipoatrophy, and lymphocytic infiltration were reduced in EL-Kras/Tgfbr1(+/-) mice. We conclude that Tgfbr1 signaling promotes the development of precancerous lesions in mice. These findings suggest that individuals with constitutively decreased TGFBR1 expression may have a decreased risk of pancreatic cancer. [Cancer Res 2009;69(24):9169-74]

引用

页码：9169 / 9174

页数：6

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