The Wnt pathway is active in a small subset of pancreas cancer cell lines.
Activation of the Wnt pathway plays an important role in the development of a wide variety of tumor types. Two genes involved in the activation of this pathway in tumors are Adenomatous Polyposis Coli (APC) and beta-catenin. Here, we analyze the activity of the Wnt pathway in cultured cells derived from ductal and acinar pancreatic adenocarcinomas using a reporter assay dependent on the activity of the beta-catenin/Tcf4 complex. We find that low-level Wnt activity can be detected in several pancreas cancer lines. High levels of reporter activity were detected exclusively in RWP-1 cells. These cells display nuclear beta-catenin and express a truncated APC protein resulting from a CAA>TAA mutation (Q1303X). Expression of a dominant negative Tcf4 protein inhibited proliferation of RWP-1 cells but not in other lines lacking beta-catenin-dependent reporter activity, supporting the functional relevance of this mutation. Our findings indicate that activation of the Wnt pathway may play a role in a small subset of ductal pancreatic cancers. Alternatively, RWP-1 cells may have been derived from a tumor arising in a structure adjacent to the pancreas such as the biliary tract or the Ampulla of Vater. Additional studies on the role of Wnt pathway components in the development/progression of tumors of the peripancreatic region merit consideration.
Pujal
Judit
J
Unitat de Biologia Cellular i Molecular, Institut Municipal d'Investigació Mèdica, Barcelona, Spain.
Capellá
Gabriel
G
Real
Francisco X
FX
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D021381:Protein Transport; D015533:Transcriptional Activation / Q000235:genetics; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D025601:Adenomatous Polyposis Coli Protein; D051153:Wnt Proteins; D051176:beta Catenin