Wang Lidong, Heidt David G, Lee Cheong J, Yang Huibin, Logsdon Craig D, Zhang Lizhi, Fearon Eric R, Ljungman Mats, Simeone Diane M
Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Cancer Cell. 2009 Mar 3;15(3):207-19. doi: 10.1016/j.ccr.2009.01.018.
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 3beta in the Wnt/beta-catenin signaling pathway.
胰腺癌是一种致命疾病，其特征为诊断延迟和对治疗产生耐药性。在确定胰腺癌的基因缺陷方面已取得很大进展，但仍有待全面阐述其分子发病机制。在此，我们表明，共济失调毛细血管扩张症D组互补基因（ATDC，也称为TRIM29）在大多数侵袭性胰腺癌和胰腺癌前病变中表达升高。ATDC在体外促进癌细胞增殖，并在体内增强肿瘤生长和转移。ATDC表达与胰腺癌中β-连环蛋白水平升高相关，且β-连环蛋白功能是ATDC致癌作用所必需的。研究发现，ATDC通过对蓬乱蛋白2（Disheveled-2）产生诱导作用来稳定β-连环蛋白，蓬乱蛋白2是Wnt/β-连环蛋白信号通路中糖原合酶激酶3β的负调节因子。
