Common Activation of Canonical Wnt Signaling in Pancreatic Adenocarcinoma

被引：173

作者：

di Magliano, Marina Pasca ^{[1
]}

Biankin, Andrew V. ^{[2
,3
]}

Heiser, Patrick W. ^{[1
]}

Cano, David A. ^{[1
]}

Gutierrez, Pedro J. A. ^{[1
]}

Deramaudt, Therese ^{[4
]}

Segara, Davendra ^{[2
]}

Dawson, Amanda C. ^{[2
]}

Kench, James G. ^{[2
]}

Henshall, Susan M. ^{[2
]}

Sutherland, Robert L. ^{[2
]}

Dlugosz, Andrzej ^{[5
]}

Rustgi, Anil K. ^{[4
]}

Hebrok, Matthias ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Med, Ctr Diabet, San Francisco, CA 94143 USA

[2] St Vincents Hosp, Garvan Inst Med Res, Canc Res Program, Darlinghurst, NSW 2010, Australia

[3] Bankstown Hosp, Dept Surg, Sydney, NSW, Australia

[4] Univ Penn, Dept Genet, Div Gastroenterol, Philadelphia, PA 19104 USA

[5] Univ Michigan, Dept Dermatol, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA

来源：

PLOS ONE | 2007年 / 2卷 / 11期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1371/journal.pone.0001155

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Pancreatic ductal adenocarcinoma (PDA) is an extremely aggressive malignancy, which carries a dismal prognosis. Activating mutations of the Kras gene are common to the vast majority of human PDA. In addition, recent studies have demonstrated that embryonic signaling pathway such as Hedgehog and Notch are inappropriately upregulated in this disease. The role of another embryonic signaling pathway, namely the canonical Wnt cascade, is still controversial. Here, we use gene array analysis as a platform to demonstrate general activation of the canonical arm of the Wnt pathway in human PDA. Furthermore, we provide evidence for Wnt activation in mouse models of pancreatic cancer. Our results also indicate that Wnt signaling might be activated downstream of Hedgehog signaling, which is an early event in PDA evolution. Wnt inhibition blocked proliferation and induced apoptosis of cultured adenocarcinoma cells, thereby providing evidence to support the development of novel therapeutical strategies for Wnt inhibition in pancreatic adenocarcinoma.

引用

页数：9

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