Oncogenic Function of ATDC in Pancreatic Cancer through Wnt Pathway Activation and β-Catenin Stabilization

被引：222

作者：

Wang, Lidong ^{[1
]}

Heidt, David G. ^{[1
]}

Lee, Cheong J. ^{[1
]}

Yang, Huibin ^{[1
]}

Logsdon, Craig D. ^{[5
]}

Zhang, Lizhi ^{[6
]}

Fearon, Eric R. ^{[3
,4
,7
]}

Ljungman, Mats ^{[2
]}

Simeone, Diane M. ^{[1
,8
]}

机构：

[1] Univ Michigan, Med Ctr, Dept Surg, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Med Ctr, Dept Radiat Oncol, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Med Ctr, Dept Pathol, Ann Arbor, MI 48109 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA

[6] Mayo Clin, Dept Pathol, Rochester, MN 55905 USA

[7] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA

[8] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA

来源：

CANCER CELL | 2009年 / 15卷 / 03期

关键词：

TELANGIECTASIA GROUP-D; GENE-EXPRESSION ANALYSIS; PROSTATE-CANCER; IN-SITU; CELLS; IDENTIFICATION; CARCINOMA; PROTEIN; ADENOCARCINOMA; METASTASIS;

D O I：

10.1016/j.ccr.2009.01.018

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Pancreatic cancer is a deadly disease characterized by late diagnosis and resistance to therapy. Much progress has been made in defining gene defects in pancreatic cancer, but a full accounting of its molecular pathogenesis remains to be provided. Here, we show that expression of the ataxia-telangiectasia. group D complementing gene (ATDC), also called TRIM29, is elevated in most invasive pancreatic cancers and pancreatic cancer precursor lesions. ATDC promoted cancer cell proliferation in vitro and enhanced tumor growth and metastasis in vivo. ATDC expression correlated with elevated beta-catenin levels in pancreatic cancer, and beta-catenin function was required for ATDC's oncogenic effects. ATDC was found to stabilize beta-catenin via ATDC-induced effects on the Disheveled-2 protein, a negative regulator of glycogen synthase kinase 3 beta in the Wnt/beta-catenin signaling pathway.

引用

页码：207 / 219

页数：13

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