Oncogenic function of ATDC in pancreatic cancer through Wnt pathway activation and beta-catenin stabilization. Cancer Cell 2009 Mar 03;15(3):207-19
Date
03/03/2009Pubmed ID
19249679Pubmed Central ID
PMC2673547DOI
10.1016/j.ccr.2009.01.018Scopus ID
2-s2.0-60649114313 (requires institutional sign-in at Scopus site) 205 CitationsAbstract
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.
Author List
Wang L, Heidt DG, Lee CJ, Yang H, Logsdon CD, Zhang L, Fearon ER, Ljungman M, Simeone DMMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAnimals
Blotting, Western
DNA-Binding Proteins
Dishevelled Proteins
Gene Expression
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Immunoprecipitation
Male
Pancreatic Neoplasms
Phosphoproteins
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Transcription Factors
Wnt Proteins
beta Catenin
